rs34437789

Variant names:

• chr8-144515758-T-A
• rs34437789
• NM_004260.4:c.1258+6A>T

Your query was ambiguous. Multiple possible variants found:

• chr8-144515758-T-A
• chr8-144515758-T-C
• chr8-144515758-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004260.4(RECQL4):​c.1258+6A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0289 in 1,611,922 control chromosomes in the GnomAD database, including 814 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (51 hom., cov: 34)
  • Exomes 𝑓: 0.030 (763 hom.)
• Consequence: RECQL4 NM_004260.4 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.371
• Publications: 9 publications found

Genes affected

RECQL4 (HGNC:9949): (RecQ like helicase 4) The protein encoded by this gene is a DNA helicase that belongs to the RecQ helicase family. DNA helicases unwind double-stranded DNA into single-stranded DNAs and may modulate chromosome segregation. This gene is predominantly expressed in thymus and testis. Mutations in this gene are associated with Rothmund-Thomson, RAPADILINO and Baller-Gerold syndromes. [provided by RefSeq, Jan 2010]

RECQL4 Gene-Disease associations (from GenCC):

• Baller-Gerold syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Orphanet
• Rothmund-Thomson syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Rothmund-Thomson syndrome type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, G2P
• osteosarcoma

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
• rapadilino syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 8-144515758-T-A is Benign according to our data. Variant chr8-144515758-T-A is described in ClinVar as Benign. ClinVar VariationId is 259257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0906 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004260.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL4	NM_004260.4	MANE Select	c.1258+6A>T		splice_region intron	N/A	NP_004251.4
	RECQL4	NM_001413019.1		c.1258+6A>T		splice_region intron	N/A	NP_001399948.1
	RECQL4	NM_001413036.1		c.1258+6A>T		splice_region intron	N/A	NP_001399965.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL4	ENST00000617875.6	TSL:1 MANE Select	c.1258+6A>T		splice_region intron	N/A	ENSP00000482313.2
	RECQL4	ENST00000621189.4	TSL:1	c.187+6A>T		splice_region intron	N/A	ENSP00000483145.1
	RECQL4	ENST00000532846.2	TSL:5	c.142+6A>T		splice_region intron	N/A	ENSP00000476551.1

Frequencies

GnomAD3 genomes AF: 0.0225 AC: 3420 AN: 152136 Hom.: 51 Cov.: 34

Gnomad AFR AF: 0.00613

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0283

Gnomad ASJ AF: 0.0573

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0110

Gnomad FIN AF: 0.00725

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0323

Gnomad OTH AF: 0.0377

GnomAD2 exomes AF: 0.0242 AC: 5958 AN: 246064 AF XY: 0.0249

Gnomad AFR exome AF: 0.00564

Gnomad AMR exome AF: 0.0202

Gnomad ASJ exome AF: 0.0547

Gnomad EAS exome AF: 0.0000558

Gnomad FIN exome AF: 0.00862

Gnomad NFE exome AF: 0.0345

Gnomad OTH exome AF: 0.0319

GnomAD4 exome AF: 0.0296 AC: 43153 AN: 1459668 Hom.: 763 Cov.: 65 AF XY: 0.0294 AC XY: 21375 AN XY: 726006

African (AFR) AF: 0.00822 AC: 275 AN: 33468

American (AMR) AF: 0.0202 AC: 902 AN: 44590

Ashkenazi Jewish (ASJ) AF: 0.0578 AC: 1508 AN: 26092

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39678

South Asian (SAS) AF: 0.0148 AC: 1273 AN: 86076

European-Finnish (FIN) AF: 0.00997 AC: 520 AN: 52178

Middle Eastern (MID) AF: 0.0973 AC: 561 AN: 5768

European-Non Finnish (NFE) AF: 0.0325 AC: 36169 AN: 1111498

Other (OTH) AF: 0.0322 AC: 1944 AN: 60320

GnomAD4 genome AF: 0.0224 AC: 3416 AN: 152254 Hom.: 51 Cov.: 34 AF XY: 0.0204 AC XY: 1520 AN XY: 74442

African (AFR) AF: 0.00609 AC: 253 AN: 41526

American (AMR) AF: 0.0283 AC: 433 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0573 AC: 199 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5180

South Asian (SAS) AF: 0.0108 AC: 52 AN: 4828

European-Finnish (FIN) AF: 0.00725 AC: 77 AN: 10616

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0323 AC: 2196 AN: 68006

Other (OTH) AF: 0.0373 AC: 79 AN: 2116

Alfa AF: 0.0310 Hom.: 28

Bravo AF: 0.0240

Asia WGS AF: 0.00866 AC: 30 AN: 3478

EpiCase AF: 0.0387

EpiControl AF: 0.0392

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

not provided Benign:3

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Sep 23, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 27247962)

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Rapadilino syndrome Benign:1

Feb 01, 2025

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Rothmund-Thomson syndrome type 2 Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Baller-Gerold syndrome Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.1
DANN	Benign	0.72
PhyloP100		-0.37
PromoterAI		0.29	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34437789; hg19: chr8-145741142; COSMIC: COSV52882091;