rs7760535

Variant names:

• chr6-111425880-G-C
• rs7760535
• NM_001372078.1:c.140-9408C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001372078.1(REV3L):​c.140-9408C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 152,030 control chromosomes in the GnomAD database, including 19,022 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 0.46 (19022 hom., cov: 32)
• Consequence: REV3L NM_001372078.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.325
• Publications: 24 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REV3L	NM_001372078.1	c.140-9408C>G		intron_variant	Intron 1 of 31	ENST00000368802.8	NP_001359007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REV3L	ENST00000368802.8	c.140-9408C>G		intron_variant	Intron 1 of 31	1	NM_001372078.1	ENSP00000357792.3

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69896 AN: 151914 Hom.: 19019 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.460 AC: 69918 AN: 152030 Hom.: 19022 Cov.: 32 AF XY: 0.457 AC XY: 33976 AN XY: 74330

African (AFR) AF: 0.156 AC: 6471 AN: 41486

American (AMR) AF: 0.482 AC: 7360 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1966 AN: 3470

East Asian (EAS) AF: 0.414 AC: 2144 AN: 5178

South Asian (SAS) AF: 0.557 AC: 2678 AN: 4812

European-Finnish (FIN) AF: 0.575 AC: 6065 AN: 10546

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.609 AC: 41404 AN: 67952

Other (OTH) AF: 0.482 AC: 1020 AN: 2116

Alfa AF: 0.555 Hom.: 12249

Bravo AF: 0.440

Asia WGS AF: 0.474 AC: 1646 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	0.57
DANN	Benign	0.32
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism (auto)

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: rs7760535; hg19: chr6-111747083; COSMIC: COSV62622829; COSMIC: COSV62622829;