chr8-144511703-C-T

Variant names:

• chr8-144511703-C-T
• rs34914400
• NM_004260.4:c.3480G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_004260.4(RECQL4):​c.3480G>A​(p.Val1160Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00283 in 1,612,562 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (54 hom., cov: 34)
  • Exomes 𝑓: 0.0016 (56 hom.)
• Consequence: RECQL4 NM_004260.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.149
• Publications: 4 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, SUPPORTIVE Submitted by: Orphanet, G2P
• Rothmund-Thomson syndrome

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

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

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

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet
• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 8-144511703-C-T is Benign according to our data. Variant chr8-144511703-C-T is described in ClinVar as Benign. ClinVar VariationId is 414191.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.149 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0526 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL4	NM_004260.4	MANE Select	c.3480G>A	p.Val1160Val	synonymous	Exon 20 of 21	NP_004251.4	O94761
	RECQL4	NM_001413019.1		c.3555G>A	p.Val1185Val	synonymous	Exon 19 of 20	NP_001399948.1
	RECQL4	NM_001413036.1		c.3489G>A	p.Val1163Val	synonymous	Exon 20 of 21	NP_001399965.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL4	ENST00000617875.6	TSL:1 MANE Select	c.3480G>A	p.Val1160Val	synonymous	Exon 20 of 21	ENSP00000482313.2	O94761
	RECQL4	ENST00000621189.4	TSL:1	c.2409G>A	p.Val803Val	synonymous	Exon 19 of 20	ENSP00000483145.1	A0A087X072
	RECQL4	ENST00000971710.1		c.3387G>A	p.Val1129Val	synonymous	Exon 20 of 21	ENSP00000641769.1

Frequencies

GnomAD3 genomes AF: 0.0143 AC: 2181 AN: 152236 Hom.: 54 Cov.: 34

Gnomad AFR AF: 0.0500

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00419

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00366 AC: 905 AN: 247534 AF XY: 0.00280

Gnomad AFR exome AF: 0.0510

Gnomad AMR exome AF: 0.00235

Gnomad ASJ exome AF: 0.00120

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000197

Gnomad OTH exome AF: 0.00133

GnomAD4 exome AF: 0.00163 AC: 2377 AN: 1460208 Hom.: 56 Cov.: 36 AF XY: 0.00140 AC XY: 1018 AN XY: 726380

African (AFR) AF: 0.0547 AC: 1830 AN: 33476

American (AMR) AF: 0.00291 AC: 130 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00157 AC: 41 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52036

Middle Eastern (MID) AF: 0.00312 AC: 18 AN: 5766

European-Non Finnish (NFE) AF: 0.000137 AC: 152 AN: 1111776

Other (OTH) AF: 0.00326 AC: 197 AN: 60344

GnomAD4 genome AF: 0.0144 AC: 2191 AN: 152354 Hom.: 54 Cov.: 34 AF XY: 0.0143 AC XY: 1064 AN XY: 74498

African (AFR) AF: 0.0501 AC: 2083 AN: 41582

American (AMR) AF: 0.00418 AC: 64 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68030

Other (OTH) AF: 0.00993 AC: 21 AN: 2114

Alfa AF: 0.00518 Hom.: 36

Bravo AF: 0.0162

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Baller-Gerold syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	7.0
DANN	Benign	0.91
PhyloP100		-0.15
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs34914400; hg19: chr8-145737086;