rs74833651

Positions:

• chr6-111466545-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001372078.1(REV3L):​c.139+16205C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0258 in 152,280 control chromosomes in the GnomAD database, including 55 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 0.026 (55 hom., cov: 33)
• Consequence: REV3L NM_001372078.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.666

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0258 (3933/152280) while in subpopulation AMR AF= 0.0346 (528/15282). AF 95% confidence interval is 0.033. There are 55 homozygotes in gnomad4. There are 1896 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3933 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REV3L	NM_001372078.1	c.139+16205C>T		intron_variant		ENST00000368802.8	NP_001359007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REV3L	ENST00000368802.8	c.139+16205C>T		intron_variant		1	NM_001372078.1	ENSP00000357792.3

Frequencies

GnomAD3 genomes AF: 0.0258 AC: 3933 AN: 152162 Hom.: 55 Cov.: 33

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0346

Gnomad ASJ AF: 0.0522

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0228

Gnomad FIN AF: 0.0182

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0341

Gnomad OTH AF: 0.0402

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

GnomAD4 genome AF: 0.0258 AC: 3933 AN: 152280 Hom.: 55 Cov.: 33 AF XY: 0.0255 AC XY: 1896 AN XY: 74482

Gnomad4 AFR AF: 0.0118

Gnomad4 AMR AF: 0.0346

Gnomad4 ASJ AF: 0.0522

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0226

Gnomad4 FIN AF: 0.0182

Gnomad4 NFE AF: 0.0342

Gnomad4 OTH AF: 0.0398

Alfa AF: 0.0260 Hom.: 8

Bravo AF: 0.0275

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.61
DANN	Benign	0.86

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: rs74833651; hg19: chr6-111787748;