rs455726

Variant names:

• chr6-111378165-G-A
• rs455726
• NM_001372078.1:c.1455-322C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-111378165-G-A
• chr6-111378165-G-C
• chr6-111378165-G-T

Variant summary

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

The NM_001372078.1(REV3L):​c.1455-322C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 151,988 control chromosomes in the GnomAD database, including 14,622 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 (14622 hom., cov: 31)
• Consequence: REV3L NM_001372078.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.664
• Publications: 10 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REV3L	NM_001372078.1	c.1455-322C>T		intron_variant	Intron 11 of 31	ENST00000368802.8	NP_001359007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REV3L	ENST00000368802.8	c.1455-322C>T		intron_variant	Intron 11 of 31	1	NM_001372078.1	ENSP00000357792.3

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60621 AN: 151872 Hom.: 14621 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: 0.411

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.399 AC: 60641 AN: 151988 Hom.: 14622 Cov.: 31 AF XY: 0.398 AC XY: 29535 AN XY: 74264

African (AFR) AF: 0.111 AC: 4612 AN: 41516

American (AMR) AF: 0.430 AC: 6561 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1484 AN: 3464

East Asian (EAS) AF: 0.412 AC: 2126 AN: 5162

South Asian (SAS) AF: 0.510 AC: 2454 AN: 4808

European-Finnish (FIN) AF: 0.498 AC: 5240 AN: 10526

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.540 AC: 36718 AN: 67942

Other (OTH) AF: 0.410 AC: 863 AN: 2106

Alfa AF: 0.484 Hom.: 54080

Bravo AF: 0.381

Asia WGS AF: 0.447 AC: 1554 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.44
DANN	Benign	0.54
PhyloP100		-0.66
Mutation Taster		=99/1	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: rs455726; hg19: chr6-111699368;