rs465969

Positions:

• chr6-111334327-G-A

Variant summary

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

The NM_001372078.1(REV3L):​c.7681-960C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0869 in 152,200 control chromosomes in the GnomAD database, including 613 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 0.087 (613 hom., cov: 32)
• Consequence: REV3L NM_001372078.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.544

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REV3L	NM_001372078.1	c.7681-960C>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.7681-960C>T		intron_variant		1	NM_001372078.1	ENSP00000357792	P4

Frequencies

GnomAD3 genomes AF: 0.0868 AC: 13208 AN: 152082 Hom.: 616 Cov.: 32

Gnomad AFR AF: 0.0908

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.0285

Gnomad SAS AF: 0.0716

Gnomad FIN AF: 0.0686

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0815

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.0869 AC: 13227 AN: 152200 Hom.: 613 Cov.: 32 AF XY: 0.0862 AC XY: 6418 AN XY: 74414

Gnomad4 AFR AF: 0.0910

Gnomad4 AMR AF: 0.115

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.0283

Gnomad4 SAS AF: 0.0712

Gnomad4 FIN AF: 0.0686

Gnomad4 NFE AF: 0.0815

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0886 Hom.: 844

Bravo AF: 0.0921

Asia WGS AF: 0.0560 AC: 196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.0
DANN	Benign	0.43

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: rs465969; hg19: chr6-111655530;