19-43575535-G-A

Variant names:

• chr19-43575535-G-A
• rs3213245
• ENST00000594374.1:c.169-14515C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000594374.1(ENSG00000268361):​c.169-14515C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 1,467,464 control chromosomes in the GnomAD database, including 274,986 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 0.61 (28318 hom., cov: 31)
  • Exomes 𝑓: 0.60 (246668 hom.)
• Consequence: ENSG00000268361 ENST00000594374.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700
• Publications: 105 publications found

Genes affected

ENSG00000268361 (HGNC:):

XRCC1 (HGNC:12828): (X-ray repair cross complementing 1) The protein encoded by this gene is involved in the efficient repair of DNA single-strand breaks formed by exposure to ionizing radiation and alkylating agents. This protein interacts with DNA ligase III, polymerase beta and poly (ADP-ribose) polymerase to participate in the base excision repair pathway. It may play a role in DNA processing during meiogenesis and recombination in germ cells. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity. [provided by RefSeq, Jul 2008]

PINLYP (HGNC:44206): (phospholipase A2 inhibitor and LY6/PLAUR domain containing) Predicted to enable phospholipase inhibitor activity. Predicted to be involved in negative regulation of catalytic activity. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000594374.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC1	NM_006297.3	MANE Select	c.-77C>T		upstream_gene	N/A	NP_006288.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000268361	ENST00000594374.1	TSL:3	c.169-14515C>T		intron	N/A	ENSP00000472698.1
	ENSG00000269583	ENST00000600242.1	TSL:4	n.463G>A		non_coding_transcript_exon	Exon 2 of 2
	XRCC1	ENST00000543982.5	TSL:2	c.-77C>T		5_prime_UTR	Exon 1 of 16	ENSP00000443671.1

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92148 AN: 151734 Hom.: 28305 Cov.: 31

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.700

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.878

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.617

GnomAD2 exomes AF: 0.650 AC: 128956 AN: 198250 AF XY: 0.641

Gnomad AFR exome AF: 0.609

Gnomad AMR exome AF: 0.803

Gnomad ASJ exome AF: 0.657

Gnomad EAS exome AF: 0.889

Gnomad FIN exome AF: 0.573

Gnomad NFE exome AF: 0.596

Gnomad OTH exome AF: 0.632

GnomAD4 exome AF: 0.604 AC: 795285 AN: 1315610 Hom.: 246668 Cov.: 18 AF XY: 0.603 AC XY: 392843 AN XY: 651374

African (AFR) AF: 0.600 AC: 17685 AN: 29458

American (AMR) AF: 0.789 AC: 29495 AN: 37406

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 15598 AN: 23736

East Asian (EAS) AF: 0.894 AC: 32760 AN: 36628

South Asian (SAS) AF: 0.613 AC: 48395 AN: 78932

European-Finnish (FIN) AF: 0.563 AC: 28775 AN: 51130

Middle Eastern (MID) AF: 0.668 AC: 3388 AN: 5070

European-Non Finnish (NFE) AF: 0.586 AC: 585658 AN: 998916

Other (OTH) AF: 0.617 AC: 33531 AN: 54334

GnomAD4 genome AF: 0.607 AC: 92204 AN: 151854 Hom.: 28318 Cov.: 31 AF XY: 0.610 AC XY: 45260 AN XY: 74200

African (AFR) AF: 0.597 AC: 24738 AN: 41442

American (AMR) AF: 0.700 AC: 10681 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 2280 AN: 3472

East Asian (EAS) AF: 0.878 AC: 4484 AN: 5106

South Asian (SAS) AF: 0.627 AC: 3025 AN: 4822

European-Finnish (FIN) AF: 0.557 AC: 5877 AN: 10548

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.576 AC: 39098 AN: 67896

Other (OTH) AF: 0.618 AC: 1301 AN: 2104

Alfa AF: 0.591 Hom.: 5052

Bravo AF: 0.624

Asia WGS AF: 0.733 AC: 2545 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.2
DANN	Benign	0.95
PhyloP100		-0.0070
PromoterAI		0.067	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3213245; hg19: chr19-44079687; COSMIC: COSV53448643; COSMIC: COSV53448643;