6-111352511-T-C

Variant names:

• chr6-111352511-T-C
• rs240993
• NM_001372078.1:c.7185-720A>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.7185-720A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 151,926 control chromosomes in the GnomAD database, including 26,211 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 0.54 (26211 hom., cov: 30)
• Consequence: REV3L NM_001372078.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 51 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REV3L	NM_001372078.1	c.7185-720A>G		intron_variant	Intron 18 of 31	ENST00000368802.8	NP_001359007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REV3L	ENST00000368802.8	c.7185-720A>G		intron_variant	Intron 18 of 31	1	NM_001372078.1	ENSP00000357792.3

Frequencies

GnomAD3 genomes AF: 0.540 AC: 82034 AN: 151808 Hom.: 26217 Cov.: 30

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.594

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.540 AC: 82039 AN: 151926 Hom.: 26211 Cov.: 30 AF XY: 0.536 AC XY: 39791 AN XY: 74228

African (AFR) AF: 0.185 AC: 7661 AN: 41434

American (AMR) AF: 0.575 AC: 8789 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 2162 AN: 3470

East Asian (EAS) AF: 0.416 AC: 2152 AN: 5168

South Asian (SAS) AF: 0.645 AC: 3100 AN: 4806

European-Finnish (FIN) AF: 0.624 AC: 6559 AN: 10514

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.731 AC: 49676 AN: 67952

Other (OTH) AF: 0.575 AC: 1212 AN: 2108

Alfa AF: 0.668 Hom.: 157252

Bravo AF: 0.519

Asia WGS AF: 0.523 AC: 1821 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.49
DANN	Benign	0.47
PhyloP100		-1.1
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: rs240993; hg19: chr6-111673714; COSMIC: COSV62622728; COSMIC: COSV62622728;