1-241848042-C-G

Variant names:

• chr1-241848042-C-G
• rs1776180
• ENST00000684005.2:n.95G>C

Variant summary

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

The ENST00000684005.2(ENSG00000288723):​n.95G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 152,168 control chromosomes in the GnomAD database, including 28,027 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 0.60 (28017 hom., cov: 33)
  • Exomes 𝑓: 0.58 (10 hom.)
• Consequence: ENSG00000288723 ENST00000684005.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 13 publications found

Genes affected

ENSG00000288723 (HGNC:):

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]

EXO1 Gene-Disease associations (from GenCC):

• Lynch syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXO1	NM_130398.4	c.-731C>G		upstream_gene_variant		ENST00000366548.8	NP_569082.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXO1	ENST00000366548.8	c.-731C>G		upstream_gene_variant		1	NM_130398.4	ENSP00000355506.3

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91523 AN: 152000 Hom.: 27989 Cov.: 33

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.674

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.605

GnomAD4 exome AF: 0.580 AC: 29 AN: 50 Hom.: 10 Cov.: 0 AF XY: 0.571 AC XY: 24 AN XY: 42

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.568 AC: 25 AN: 44

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.602 AC: 91599 AN: 152118 Hom.: 28017 Cov.: 33 AF XY: 0.606 AC XY: 45079 AN XY: 74358

African (AFR) AF: 0.655 AC: 27219 AN: 41528

American (AMR) AF: 0.675 AC: 10320 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1511 AN: 3466

East Asian (EAS) AF: 0.798 AC: 4100 AN: 5140

South Asian (SAS) AF: 0.537 AC: 2591 AN: 4822

European-Finnish (FIN) AF: 0.603 AC: 6374 AN: 10574

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.553 AC: 37560 AN: 67980

Other (OTH) AF: 0.607 AC: 1279 AN: 2108

Alfa AF: 0.481 Hom.: 1446

Bravo AF: 0.611

Asia WGS AF: 0.666 AC: 2315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.32
DANN	Benign	0.39
PhyloP100		-1.2
PromoterAI		0.0063	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1776180; hg19: chr1-242011344; COSMIC: COSV62218937;