rs1989574

Variant names:

• chr6-111407330-T-C
• rs1989574
• NM_001372078.1:c.405-1700A>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.405-1700A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 151,896 control chromosomes in the GnomAD database, including 14,652 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 0.40 (14652 hom., cov: 31)
• Consequence: REV3L NM_001372078.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368
• Publications: 7 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]

ENSG00000295830 (HGNC:):

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 = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REV3L	NM_001372078.1	c.405-1700A>G		intron_variant	Intron 3 of 31	ENST00000368802.8	NP_001359007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REV3L	ENST00000368802.8	c.405-1700A>G		intron_variant	Intron 3 of 31	1	NM_001372078.1	ENSP00000357792.3

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60687 AN: 151778 Hom.: 14650 Cov.: 31

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.381

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.400 AC: 60708 AN: 151896 Hom.: 14652 Cov.: 31 AF XY: 0.398 AC XY: 29558 AN XY: 74240

African (AFR) AF: 0.111 AC: 4606 AN: 41428

American (AMR) AF: 0.431 AC: 6577 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1485 AN: 3470

East Asian (EAS) AF: 0.414 AC: 2131 AN: 5150

South Asian (SAS) AF: 0.510 AC: 2451 AN: 4806

European-Finnish (FIN) AF: 0.498 AC: 5239 AN: 10526

Middle Eastern (MID) AF: 0.407 AC: 118 AN: 290

European-Non Finnish (NFE) AF: 0.541 AC: 36784 AN: 67934

Other (OTH) AF: 0.407 AC: 857 AN: 2104

Alfa AF: 0.473 Hom.: 4886

Bravo AF: 0.381

Asia WGS AF: 0.448 AC: 1557 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	1.2
DANN	Benign	0.49
PhyloP100		-0.37
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: rs1989574; hg19: chr6-111728533;