rs459809

Positions:

• chr6-111331964-T-C

Variant summary

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

The NM_001372078.1(REV3L):​c.7926-180A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.71 in 152,122 control chromosomes in the GnomAD database, including 39,447 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 0.71 (39447 hom., cov: 33)
• Consequence: REV3L NM_001372078.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.657

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REV3L	NM_001372078.1	c.7926-180A>G		intron_variant		ENST00000368802.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REV3L	ENST00000368802.8	c.7926-180A>G		intron_variant		1	NM_001372078.1	P4

Frequencies

GnomAD3 genomes AF: 0.710 AC: 107891 AN: 152004 Hom.: 39436 Cov.: 33

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.724

Gnomad ASJ AF: 0.786

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.745

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.736

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

GnomAD4 genome AF: 0.710 AC: 107951 AN: 152122 Hom.: 39447 Cov.: 33 AF XY: 0.704 AC XY: 52354 AN XY: 74362

Gnomad4 AFR AF: 0.562

Gnomad4 AMR AF: 0.724

Gnomad4 ASJ AF: 0.786

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.716

Gnomad4 FIN AF: 0.694

Gnomad4 NFE AF: 0.814

Gnomad4 OTH AF: 0.732

Alfa AF: 0.753 Hom.: 6400

Bravo AF: 0.706

Asia WGS AF: 0.599 AC: 2083 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.77

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: rs459809; hg19: chr6-111653167; COSMIC: COSV62622689;