6-43610271-GC-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_006502.3(POLH):c.1075-281del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 151,884 control chromosomes in the GnomAD database, including 22 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.013 (22 hom., cov: 31)
• Consequence: POLH NM_006502.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.561

Genes affected

POLH (HGNC:9181): (DNA polymerase eta) This gene encodes a member of the Y family of specialized DNA polymerases. It copies undamaged DNA with a lower fidelity than other DNA-directed polymerases. However, it accurately replicates UV-damaged DNA; when thymine dimers are present, this polymerase inserts the complementary nucleotides in the newly synthesized DNA, thereby bypassing the lesion and suppressing the mutagenic effect of UV-induced DNA damage. This polymerase is thought to be involved in hypermutation during immunoglobulin class switch recombination. Mutations in this gene result in XPV, a variant type of xeroderma pigmentosum. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]

POLR1C (HGNC:):

GTPBP2 (HGNC:4670): (GTP binding protein 2) GTP-binding proteins, or G proteins, constitute a superfamily capable of binding GTP or GDP. G proteins are activated by binding GTP and are inactivated by hydrolyzing GTP to GDP. This general mechanism enables G proteins to perform a wide range of biologic activities.[supplied by OMIM, Jan 2003]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 6-43610271-GC-G is Benign according to our data. Variant chr6-43610271-GC-G is described in ClinVar as [Likely_benign]. Clinvar id is 1197500.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.013 (1975/151884) while in subpopulation NFE AF= 0.0213 (1446/67956). AF 95% confidence interval is 0.0204. There are 22 homozygotes in gnomad4. There are 908 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLH	NM_006502.3	c.1075-281del		intron_variant		ENST00000372236.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLH	ENST00000372236.9	c.1075-281del		intron_variant		1	NM_006502.3	P1
POLH	ENST00000372226.1	c.1075-281del		intron_variant		1
GTPBP2	ENST00000496137.5	c.*132-4890del		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0130 AC: 1975 AN: 151766 Hom.: 22 Cov.: 31

Gnomad AFR AF: 0.00358

Gnomad AMI AF: 0.0793

Gnomad AMR AF: 0.00696

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00396

Gnomad FIN AF: 0.00977

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0213

Gnomad OTH AF: 0.0110

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

GnomAD4 genome AF: 0.0130 AC: 1975 AN: 151884 Hom.: 22 Cov.: 31 AF XY: 0.0122 AC XY: 908 AN XY: 74202

Gnomad4 AFR AF: 0.00357

Gnomad4 AMR AF: 0.00689

Gnomad4 ASJ AF: 0.0170

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00397

Gnomad4 FIN AF: 0.00977

Gnomad4 NFE AF: 0.0213

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.0150 Hom.: 1

Bravo AF: 0.0128

Asia WGS AF: 0.00289 AC: 11 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs201908220; hg19: chr6-43578008;