1-241885643-C-T

Variant names:

• chr1-241885643-C-T
• rs1635488
• NM_130398.4:c.2405+136C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130398.4. 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
	EXO1	NM_130398.4	MANE Select	c.2405+136C>T		intron	N/A	NP_569082.2	Q9UQ84-1
	EXO1	NM_006027.4		c.2405+136C>T		intron	N/A	NP_006018.4	Q9UQ84-1
	EXO1	NM_001319224.2		c.2402+136C>T		intron	N/A	NP_001306153.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXO1	ENST00000366548.8	TSL:1 MANE Select	c.2405+136C>T		intron	N/A	ENSP00000355506.3	Q9UQ84-1
	EXO1	ENST00000348581.9	TSL:1	c.2405+136C>T		intron	N/A	ENSP00000311873.5	Q9UQ84-1
	EXO1	ENST00000518483.5	TSL:1	c.2405+136C>T		intron	N/A	ENSP00000430251.1	Q9UQ84-4

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

GnomAD2 exomes AF: 0.517 AC: 113278 AN: 219058 AF XY: 0.525

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 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

African (AFR) AF: 0.391 AC: 6327 AN: 16190

American (AMR) AF: 0.451 AC: 17844 AN: 39574

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 9116 AN: 19502

East Asian (EAS) AF: 0.428 AC: 14372 AN: 33606

South Asian (SAS) AF: 0.549 AC: 35895 AN: 65354

European-Finnish (FIN) AF: 0.607 AC: 22042 AN: 36320

Middle Eastern (MID) AF: 0.546 AC: 1251 AN: 2292

European-Non Finnish (NFE) AF: 0.557 AC: 195911 AN: 351486

Other (OTH) AF: 0.529 AC: 16312 AN: 30842

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

African (AFR) AF: 0.392 AC: 16221 AN: 41376

American (AMR) AF: 0.458 AC: 6986 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1719 AN: 3468

East Asian (EAS) AF: 0.412 AC: 2123 AN: 5156

South Asian (SAS) AF: 0.547 AC: 2630 AN: 4806

European-Finnish (FIN) AF: 0.611 AC: 6408 AN: 10490

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.555 AC: 37689 AN: 67918

Other (OTH) AF: 0.487 AC: 1024 AN: 2104

Alfa AF: 0.505 Hom.: 13037

Bravo AF: 0.474

Asia WGS AF: 0.465 AC: 1615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.86
DANN	Benign	0.26
PhyloP100		-0.59
Mutation Taster		=100/0	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: rs1635488; hg19: chr1-242048945; COSMIC: COSV62217782;