rs5743185

chr2-189873112-G-A

Variant summary

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

The NM_000534.5(PMS1):c.2474-384G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0596 in 152,220 control chromosomes in the GnomAD database, including 384 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 0.060 (384 hom., cov: 32)
• Consequence: PMS1 NM_000534.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

Genes affected

PMS1 (HGNC:9121): (PMS1 homolog 1, mismatch repair system component) This gene encodes a protein belonging to the DNA mismatch repair mutL/hexB family. This protein is thought to be involved in the repair of DNA mismatches, and it can form heterodimers with MLH1, a known DNA mismatch repair protein. Mutations in this gene cause hereditary nonpolyposis colorectal cancer type 3 (HNPCC3) either alone or in combination with mutations in other genes involved in the HNPCC phenotype, which is also known as Lynch syndrome. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.09 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PMS1	NM_000534.5	c.2474-384G>A		intron_variant		ENST00000441310.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PMS1	ENST00000441310.7	c.2474-384G>A		intron_variant		1	NM_000534.5	P1

Frequencies

GnomAD3 genomes AF: 0.0596 AC: 9066 AN: 152102 Hom.: 384 Cov.: 32

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0543

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.0201

Gnomad FIN AF: 0.0479

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0919

Gnomad OTH AF: 0.0641

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0596 AC: 9066 AN: 152220 Hom.: 384 Cov.: 32 AF XY: 0.0570 AC XY: 4243 AN XY: 74412

Gnomad4 AFR AF: 0.0175

Gnomad4 AMR AF: 0.0543

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0201

Gnomad4 FIN AF: 0.0479

Gnomad4 NFE AF: 0.0919

Gnomad4 OTH AF: 0.0634

Alfa AF: 0.0694 Hom.: 91

Bravo AF: 0.0580

Asia WGS AF: 0.0100 AC: 37 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	0.45
Dann	Benign	0.84

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: rs5743185; hg19: chr2-190737838;