NM_004260.4:c.2463+16C>A

Variant names:

• chr8-144513202-G-T
• rs747029514
• NM_004260.4:c.2463+16C>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004260.4(RECQL4):​c.2463+16C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00758 in 1,534,620 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0071 (9 hom., cov: 33)
  • Exomes 𝑓: 0.0076 (79 hom.)
• Consequence: RECQL4 NM_004260.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.44
• Publications: 1 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

ENSG00000265393 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 8-144513202-G-T is Benign according to our data. Variant chr8-144513202-G-T is described in ClinVar as Benign. ClinVar VariationId is 445471.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00707 (1070/151316) while in subpopulation AMR AF = 0.0114 (174/15226). AF 95% confidence interval is 0.01. There are 9 homozygotes in GnomAd4. There are 566 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL4	NM_004260.4	MANE Select	c.2463+16C>A		intron	N/A	NP_004251.4
	RECQL4	NM_001413019.1		c.2463+16C>A		intron	N/A	NP_001399948.1
	RECQL4	NM_001413036.1		c.2463+16C>A		intron	N/A	NP_001399965.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL4	ENST00000617875.6	TSL:1 MANE Select	c.2463+16C>A		intron	N/A	ENSP00000482313.2
	RECQL4	ENST00000621189.4	TSL:1	c.1392+16C>A		intron	N/A	ENSP00000483145.1
	RECQL4	ENST00000971710.1		c.2370+16C>A		intron	N/A	ENSP00000641769.1

Frequencies

GnomAD3 genomes AF: 0.00708 AC: 1070 AN: 151216 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.00155

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0114

Gnomad ASJ AF: 0.00348

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000626

Gnomad FIN AF: 0.0214

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00854

Gnomad OTH AF: 0.00725

GnomAD2 exomes AF: 0.0131 AC: 1477 AN: 112448 AF XY: 0.0131

Gnomad AFR exome AF: 0.00241

Gnomad AMR exome AF: 0.0125

Gnomad ASJ exome AF: 0.00971

Gnomad EAS exome AF: 0.00117

Gnomad FIN exome AF: 0.0450

Gnomad NFE exome AF: 0.0171

Gnomad OTH exome AF: 0.0177

GnomAD4 exome AF: 0.00763 AC: 10556 AN: 1383304 Hom.: 79 Cov.: 50 AF XY: 0.00753 AC XY: 5142 AN XY: 682504

African (AFR) AF: 0.00129 AC: 42 AN: 32598

American (AMR) AF: 0.00854 AC: 357 AN: 41812

Ashkenazi Jewish (ASJ) AF: 0.00438 AC: 103 AN: 23490

East Asian (EAS) AF: 0.000239 AC: 9 AN: 37708

South Asian (SAS) AF: 0.00113 AC: 88 AN: 77752

European-Finnish (FIN) AF: 0.0237 AC: 834 AN: 35256

Middle Eastern (MID) AF: 0.00198 AC: 10 AN: 5044

European-Non Finnish (NFE) AF: 0.00814 AC: 8731 AN: 1072314

Other (OTH) AF: 0.00666 AC: 382 AN: 57330

GnomAD4 genome AF: 0.00707 AC: 1070 AN: 151316 Hom.: 9 Cov.: 33 AF XY: 0.00766 AC XY: 566 AN XY: 73904

African (AFR) AF: 0.00154 AC: 64 AN: 41426

American (AMR) AF: 0.0114 AC: 174 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.00348 AC: 12 AN: 3446

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5134

South Asian (SAS) AF: 0.000626 AC: 3 AN: 4792

European-Finnish (FIN) AF: 0.0214 AC: 224 AN: 10478

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00855 AC: 577 AN: 67520

Other (OTH) AF: 0.00718 AC: 15 AN: 2088

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.064
DANN	Benign	0.57
PhyloP100		-1.4
PromoterAI		0.010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs747029514; hg19: chr8-145738585; COSMIC: COSV99466964; COSMIC: COSV99466964;