dbSNP rs465646: REV3L:n.1991C>T (chr6-111299555-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000462119.5(REV3L):n.1991C>T variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.806 in 152,736 control chromosomes in the GnomAD database, including 49,778 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 0.81 ( 49604 hom., cov: 34)

Exomes 𝑓: 0.81 ( 174 hom. )

Consequence

REV3L
ENST00000462119.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.43

Publications

29 publications found

Variant links:

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]

REV3L links:

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]

MFSD4B links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REV3L	NM_001372078.1 link	c.*461C>T		3_prime_UTR_variant	Exon 32 of 32	ENST00000368802.8	NP_001359007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REV3L	ENST00000368802.8 link	c.*461C>T		3_prime_UTR_variant	Exon 32 of 32	1	NM_001372078.1	ENSP00000357792.3

Frequencies

GnomAD3 genomes

AF:

0.806

AC:

122554

AN:

152084

Hom.:

49570

Cov.:

show subpopulations

Gnomad AFR

AF:

0.739

Gnomad AMI

AF:

0.816

Gnomad AMR

AF:

0.841

Gnomad ASJ

AF:

0.852

Gnomad EAS

AF:

0.800

Gnomad SAS

AF:

0.781

Gnomad FIN

AF:

0.788

Gnomad MID

AF:

0.807

Gnomad NFE

AF:

0.841

Gnomad OTH

AF:

0.829

GnomAD4 exome

AF:

0.807

AC:

431

AN:

534

Hom.:

174

Cov.:

AF XY:

0.805

AC XY:

248

AN XY:

308

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.792

AC:

336

AN:

424

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.867

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.806

AC:

122646

AN:

152202

Hom.:

49604

Cov.:

AF XY:

0.803

AC XY:

59787

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.739

AC:

30672

AN:

41514

American (AMR)

AF:

0.841

AC:

12866

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.852

AC:

2956

AN:

3470

East Asian (EAS)

AF:

0.801

AC:

4154

AN:

5188

South Asian (SAS)

AF:

0.781

AC:

3766

AN:

4822

European-Finnish (FIN)

AF:

0.788

AC:

8332

AN:

10580

Middle Eastern (MID)

AF:

0.820

AC:

241

AN:

294

European-Non Finnish (NFE)

AF:

0.841

AC:

57172

AN:

68018

Other (OTH)

AF:

0.826

AC:

1743

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1257

2515

3772

5030

6287

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

874

1748

2622

3496

4370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.830

Hom.:

144526

Bravo

AF:

0.807

Asia WGS

AF:

0.814

AC:

2829

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

4.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over