6-111331964-T-C

Variant names:

• chr6-111331964-T-C
• rs459809
• NM_001372078.1:c.7926-180A>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.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
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372078.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REV3L	NM_001372078.1	MANE Select	c.7926-180A>G		intron	N/A	NP_001359007.1
	REV3L	NM_002912.5		c.7926-180A>G		intron	N/A	NP_002903.3
	REV3L	NM_001286431.2		c.7692-180A>G		intron	N/A	NP_001273360.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REV3L	ENST00000368802.8	TSL:1 MANE Select	c.7926-180A>G		intron	N/A	ENSP00000357792.3
	REV3L	ENST00000358835.7	TSL:5	c.7926-180A>G		intron	N/A	ENSP00000351697.3
	REV3L	ENST00000435970.5	TSL:2	c.7692-180A>G		intron	N/A	ENSP00000402003.1

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

African (AFR) AF: 0.562 AC: 23285 AN: 41468

American (AMR) AF: 0.724 AC: 11065 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.786 AC: 2730 AN: 3472

East Asian (EAS) AF: 0.447 AC: 2314 AN: 5182

South Asian (SAS) AF: 0.716 AC: 3453 AN: 4820

European-Finnish (FIN) AF: 0.694 AC: 7337 AN: 10574

Middle Eastern (MID) AF: 0.753 AC: 220 AN: 292

European-Non Finnish (NFE) AF: 0.814 AC: 55331 AN: 68010

Other (OTH) AF: 0.732 AC: 1544 AN: 2108

Alfa AF: 0.761 Hom.: 11899

Bravo AF: 0.706

Asia WGS AF: 0.599 AC: 2083 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.77
PhyloP100		-0.66
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: rs459809; hg19: chr6-111653167; COSMIC: COSV62622689;