rs376447275

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_006502.3(POLH):​c.1074+11C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000991 in 1,514,050 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000096 ( 2 hom. )

Consequence

POLH
NM_006502.3 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.425
Variant links:
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
Variant 6-43605330-C-A is Benign according to our data. Variant chr6-43605330-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2955749.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000125 (19/151612) while in subpopulation SAS AF= 0.00187 (9/4818). AF 95% confidence interval is 0.000974. There are 0 homozygotes in gnomad4. There are 13 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
POLHNM_006502.3 linkc.1074+11C>A intron_variant Intron 9 of 10 ENST00000372236.9 NP_006493.1 Q9Y253-1A0A024RD62
POLHNM_001291969.2 linkc.702+11C>A intron_variant Intron 7 of 8 NP_001278898.1 B3KN75
POLHNM_001291970.2 linkc.1074+11C>A intron_variant Intron 9 of 10 NP_001278899.1 Q9Y253-2
POLHXM_047418900.1 linkc.618+11C>A intron_variant Intron 6 of 7 XP_047274856.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
POLHENST00000372236.9 linkc.1074+11C>A intron_variant Intron 9 of 10 1 NM_006502.3 ENSP00000361310.4 Q9Y253-1
POLHENST00000372226.1 linkc.1074+11C>A intron_variant Intron 9 of 10 1 ENSP00000361300.1 Q9Y253-2
GTPBP2ENST00000496137.5 linkn.*184G>T non_coding_transcript_exon_variant Exon 4 of 4 3 ENSP00000436973.1 H0YF05
GTPBP2ENST00000496137.5 linkn.*184G>T 3_prime_UTR_variant Exon 4 of 4 3 ENSP00000436973.1 H0YF05

Frequencies

GnomAD3 genomes
AF:
0.000119
AC:
18
AN:
151498
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00166
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000169
AC:
41
AN:
242228
Hom.:
0
AF XY:
0.000252
AC XY:
33
AN XY:
130740
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000296
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000956
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000111
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000962
AC:
131
AN:
1362438
Hom.:
2
Cov.:
21
AF XY:
0.000138
AC XY:
94
AN XY:
683086
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000227
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000900
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000459
Gnomad4 OTH exome
AF:
0.0000703
GnomAD4 genome
AF:
0.000125
AC:
19
AN:
151612
Hom.:
0
Cov.:
32
AF XY:
0.000176
AC XY:
13
AN XY:
74042
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00187
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000975
Hom.:
0
Bravo
AF:
0.0000793
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Feb 14, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.43
CADD
Benign
11
DANN
Benign
0.79

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs376447275; hg19: chr6-43573067; API