rs1002481

Positions:

• chr6-111390819-T-A
• chr6-111390819-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001372078.1(REV3L):​c.663-639A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 152,130 control chromosomes in the GnomAD database, including 55,998 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.86 (55998 hom., cov: 30)
• Consequence: REV3L NM_001372078.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.209

Genes affected

REV3L (HGNC:9968): (REV3 like, DNA directed polymerase zeta catalytic subunit) The protein encoded by this gene represents the catalytic subunit of DNA polymerase zeta, which functions in translesion DNA synthesis. The encoded protein can be found in mitochondria, where it protects DNA from damage. Defects in this gene are a cause of Mobius syndrome. [provided by RefSeq, Jan 2017]

MFSD4B (HGNC:21053): (major facilitator superfamily domain containing 4B) Predicted to enable glucose transmembrane transporter activity. Predicted to be involved in glucose transmembrane transport and sodium ion transport. Predicted to be located in apical plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REV3L	NM_001372078.1	c.663-639A>T		intron_variant		ENST00000368802.8	NP_001359007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REV3L	ENST00000368802.8	c.663-639A>T		intron_variant		1	NM_001372078.1	ENSP00000357792	P4

Frequencies

GnomAD3 genomes AF: 0.857 AC: 130207 AN: 152012 Hom.: 55940 Cov.: 30

Gnomad AFR AF: 0.914

Gnomad AMI AF: 0.816

Gnomad AMR AF: 0.860

Gnomad ASJ AF: 0.851

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.842

Gnomad OTH AF: 0.867

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.857 AC: 130323 AN: 152130 Hom.: 55998 Cov.: 30 AF XY: 0.853 AC XY: 63404 AN XY: 74354

Gnomad4 AFR AF: 0.914

Gnomad4 AMR AF: 0.860

Gnomad4 ASJ AF: 0.851

Gnomad4 EAS AF: 0.802

Gnomad4 SAS AF: 0.780

Gnomad4 FIN AF: 0.788

Gnomad4 NFE AF: 0.842

Gnomad4 OTH AF: 0.865

Alfa AF: 0.847 Hom.: 6372

Bravo AF: 0.866

Asia WGS AF: 0.825 AC: 2867 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	8.3
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs1002481; hg19: chr6-111712022; COSMIC: COSV62622792; COSMIC: COSV62622792;