NM_006297.3:c.-1C>T

Variant names:

• chr19-43575459-G-A
• rs2307187
• NM_006297.3:c.-1C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6 BA1

The NM_006297.3(XRCC1):​c.-1C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.015 in 1,612,136 control chromosomes in the GnomAD database, including 271 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.021 (48 hom., cov: 32)
  • Exomes 𝑓: 0.014 (223 hom.)
• Consequence: XRCC1 NM_006297.3 5_prime_UTR
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.46
• Publications: 9 publications found

Genes affected

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]

ENSG00000268361 (HGNC:):

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 19-43575459-G-A is Benign according to our data. Variant chr19-43575459-G-A is described in ClinVar as Benign. ClinVar VariationId is 3060460.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0512 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006297.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC1	NM_006297.3	MANE Select	c.-1C>T		5_prime_UTR	Exon 1 of 17	NP_006288.2	P18887

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC1	ENST00000262887.10	TSL:1 MANE Select	c.-1C>T		5_prime_UTR	Exon 1 of 17	ENSP00000262887.5	P18887
	ENSG00000268361	ENST00000594374.1	TSL:3	c.169-14439C>T		intron	N/A	ENSP00000472698.1	M0R2N6
	XRCC1	ENST00000953258.1		c.-1C>T		5_prime_UTR	Exon 1 of 17	ENSP00000623317.1

Frequencies

GnomAD3 genomes AF: 0.0214 AC: 3256 AN: 152194 Hom.: 48 Cov.: 32

Gnomad AFR AF: 0.0364

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0285

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0168

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0154

Gnomad OTH AF: 0.0234

GnomAD2 exomes AF: 0.0148 AC: 3686 AN: 249656 AF XY: 0.0151

Gnomad AFR exome AF: 0.0371

Gnomad AMR exome AF: 0.0138

Gnomad ASJ exome AF: 0.0251

Gnomad EAS exome AF: 0.000164

Gnomad FIN exome AF: 0.00158

Gnomad NFE exome AF: 0.0150

Gnomad OTH exome AF: 0.0241

GnomAD4 exome AF: 0.0143 AC: 20942 AN: 1459824 Hom.: 223 Cov.: 32 AF XY: 0.0144 AC XY: 10432 AN XY: 726060

African (AFR) AF: 0.0421 AC: 1407 AN: 33438

American (AMR) AF: 0.0158 AC: 706 AN: 44596

Ashkenazi Jewish (ASJ) AF: 0.0257 AC: 671 AN: 26088

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39626

South Asian (SAS) AF: 0.0172 AC: 1477 AN: 86064

European-Finnish (FIN) AF: 0.00210 AC: 112 AN: 53380

Middle Eastern (MID) AF: 0.0563 AC: 324 AN: 5758

European-Non Finnish (NFE) AF: 0.0136 AC: 15057 AN: 1110622

Other (OTH) AF: 0.0197 AC: 1186 AN: 60252

GnomAD4 genome AF: 0.0214 AC: 3262 AN: 152312 Hom.: 48 Cov.: 32 AF XY: 0.0210 AC XY: 1565 AN XY: 74486

African (AFR) AF: 0.0364 AC: 1515 AN: 41568

American (AMR) AF: 0.0285 AC: 436 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0222 AC: 77 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5190

South Asian (SAS) AF: 0.0170 AC: 82 AN: 4824

European-Finnish (FIN) AF: 0.00151 AC: 16 AN: 10612

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0155 AC: 1051 AN: 68022

Other (OTH) AF: 0.0232 AC: 49 AN: 2114

Alfa AF: 0.0197 Hom.: 63

Bravo AF: 0.0249

Asia WGS AF: 0.00895 AC: 32 AN: 3478

EpiCase AF: 0.0177

EpiControl AF: 0.0177

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	XRCC1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	18
DANN	Benign	0.89
PhyloP100		2.5
PromoterAI		-0.041	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Mutation Taster		=298/2	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: rs2307187; hg19: chr19-44079611; COSMIC: COSV53450509;