8-144511434-G-A

Variant names:

• chr8-144511434-G-A
• rs56341125
• NM_004260.4:c.3624C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_004260.4(RECQL4):​c.3624C>T​(p.Arg1208Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000701 in 1,612,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. R1208R) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00036 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: RECQL4 NM_004260.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.81
• Publications: 2 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]

SLC33A2 (HGNC:25157): (major facilitator superfamily domain containing 3) Predicted to enable solute:proton symporter activity. Predicted to be involved in proton transmembrane transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 8-144511434-G-A is Benign according to our data. Variant chr8-144511434-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 695611.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.81 with no splicing effect.

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.3624C>T	p.Arg1208Arg	synonymous	Exon 21 of 21	NP_004251.4	O94761
	RECQL4	NM_001413019.1		c.3699C>T	p.Arg1233Arg	synonymous	Exon 20 of 20	NP_001399948.1
	RECQL4	NM_001413036.1		c.3633C>T	p.Arg1211Arg	synonymous	Exon 21 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.3624C>T	p.Arg1208Arg	synonymous	Exon 21 of 21	ENSP00000482313.2	O94761
	RECQL4	ENST00000621189.4	TSL:1	c.2553C>T	p.Arg851Arg	synonymous	Exon 20 of 20	ENSP00000483145.1	A0A087X072
	RECQL4	ENST00000971710.1		c.3531C>T	p.Arg1177Arg	synonymous	Exon 21 of 21	ENSP00000641769.1

Frequencies

GnomAD3 genomes AF: 0.000361 AC: 55 AN: 152248 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000968 AC: 24 AN: 247902 AF XY: 0.0000666

Gnomad AFR exome AF: 0.00156

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000397 AC: 58 AN: 1460018 Hom.: 0 Cov.: 32 AF XY: 0.0000303 AC XY: 22 AN XY: 726228

African (AFR) AF: 0.00152 AC: 51 AN: 33478

American (AMR) AF: 0.0000447 AC: 2 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52068

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111582

Other (OTH) AF: 0.0000829 AC: 5 AN: 60342

GnomAD4 genome AF: 0.000361 AC: 55 AN: 152366 Hom.: 0 Cov.: 34 AF XY: 0.000336 AC XY: 25 AN XY: 74500

African (AFR) AF: 0.00130 AC: 54 AN: 41592

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000525

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Baller-Gerold syndrome (1)
-	-	1	Hereditary cancer-predisposing syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.77
DANN	Benign	0.70
PhyloP100		1.8
Mutation Taster		=100/0	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: rs56341125; hg19: chr8-145736817;