1-241885643-C-T

Position:

• chr1-241885643-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_130398.4(EXO1):​c.2405+136C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 746,952 control chromosomes in the GnomAD database, including 105,922 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 0.50 (19158 hom., cov: 30)
  • Exomes 𝑓: 0.54 (86764 hom.)
• Consequence: EXO1 NM_130398.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.587

Genes affected

EXO1 (HGNC:3511): (exonuclease 1) This gene encodes a protein with 5' to 3' exonuclease activity as well as an RNase H activity. It is similar to the Saccharomyces cerevisiae protein Exo1 which interacts with Msh2 and which is involved in mismatch repair and recombination. Alternative splicing of this gene results in three transcript variants encoding two different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXO1	NM_130398.4	c.2405+136C>T		intron_variant		ENST00000366548.8	NP_569082.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXO1	ENST00000366548.8	c.2405+136C>T		intron_variant		1	NM_130398.4	ENSP00000355506	P2

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75334 AN: 151668 Hom.: 19150 Cov.: 30

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.486

GnomAD3 exomes AF: 0.517 AC: 113278 AN: 219058 Hom.: 29690 AF XY: 0.525 AC XY: 63362 AN XY: 120598

Gnomad AFR exome AF: 0.383

Gnomad AMR exome AF: 0.448

Gnomad ASJ exome AF: 0.466

Gnomad EAS exome AF: 0.428

Gnomad SAS exome AF: 0.544

Gnomad FIN exome AF: 0.605

Gnomad NFE exome AF: 0.558

Gnomad OTH exome AF: 0.521

GnomAD4 exome AF: 0.536 AC: 319070 AN: 595166 Hom.: 86764 Cov.: 7 AF XY: 0.539 AC XY: 175648 AN XY: 325594

Gnomad4 AFR exome AF: 0.391

Gnomad4 AMR exome AF: 0.451

Gnomad4 ASJ exome AF: 0.467

Gnomad4 EAS exome AF: 0.428

Gnomad4 SAS exome AF: 0.549

Gnomad4 FIN exome AF: 0.607

Gnomad4 NFE exome AF: 0.557

Gnomad4 OTH exome AF: 0.529

GnomAD4 genome AF: 0.497 AC: 75369 AN: 151786 Hom.: 19158 Cov.: 30 AF XY: 0.496 AC XY: 36830 AN XY: 74184

Gnomad4 AFR AF: 0.392

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.496

Gnomad4 EAS AF: 0.412

Gnomad4 SAS AF: 0.547

Gnomad4 FIN AF: 0.611

Gnomad4 NFE AF: 0.555

Gnomad4 OTH AF: 0.487

Alfa AF: 0.515 Hom.: 8787

Bravo AF: 0.474

Asia WGS AF: 0.465 AC: 1615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.86
DANN	Benign	0.26

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: rs1635488; hg19: chr1-242048945; COSMIC: COSV62217782;