rs17511504

Positions:

• chr6-111309324-G-A

Variant summary

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

The ENST00000368802.8(REV3L):​c.9042+529C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0219 in 152,386 control chromosomes in the GnomAD database, including 53 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 0.022 (53 hom., cov: 31)
  • Exomes 𝑓: 0.027 (0 hom.)
• Consequence: REV3L ENST00000368802.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252

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]

(HGNC:):

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0219 (3333/152086) while in subpopulation NFE AF= 0.0324 (2203/67958). AF 95% confidence interval is 0.0313. There are 53 homozygotes in gnomad4. There are 1596 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3333 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REV3L	NM_001372078.1	c.9042+529C>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.9042+529C>T		intron_variant		1	NM_001372078.1	ENSP00000357792	P4
	ENST00000607434.1	n.122G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0219 AC: 3334 AN: 151968 Hom.: 53 Cov.: 31

Gnomad AFR AF: 0.00606

Gnomad AMI AF: 0.00659

Gnomad AMR AF: 0.0308

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00500

Gnomad FIN AF: 0.0181

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0324

Gnomad OTH AF: 0.0307

GnomAD4 exome AF: 0.0267 AC: 8 AN: 300 Hom.: 0 Cov.: 0 AF XY: 0.0194 AC XY: 4 AN XY: 206

Gnomad4 AFR exome AF: 0.0714

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0240

Gnomad4 OTH exome AF: 0.0625

GnomAD4 genome AF: 0.0219 AC: 3333 AN: 152086 Hom.: 53 Cov.: 31 AF XY: 0.0215 AC XY: 1596 AN XY: 74358

Gnomad4 AFR AF: 0.00604

Gnomad4 AMR AF: 0.0307

Gnomad4 ASJ AF: 0.0323

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00500

Gnomad4 FIN AF: 0.0181

Gnomad4 NFE AF: 0.0324

Gnomad4 OTH AF: 0.0303

Alfa AF: 0.0232 Hom.: 7

Bravo AF: 0.0238

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.4
DANN	Benign	0.82

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: rs17511504; hg19: chr6-111630527;