rs985937

Positions:

• chr6-100093311-A-G
• chr6-100093311-A-T

Variant summary

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

The ENST00000612765.1(ENSG00000275716):​n.458T>C variant causes a splice region, non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.651 in 342,420 control chromosomes in the GnomAD database, including 73,869 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 0.66 (33928 hom., cov: 30)
  • Exomes 𝑓: 0.64 (39941 hom.)
• Consequence: ENSG00000275716 ENST00000612765.1 splice_region, non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0510

Genes affected

ENSG00000275716 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC100420742		n.100093311A>G		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000275716	ENST00000612765.1	n.458T>C		splice_region_variant, non_coding_transcript_exon_variant	1/1	6
MCHR2-AS1	ENST00000661108.1	n.345-14198A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100733 AN: 151680 Hom.: 33881 Cov.: 30

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.750

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.658

GnomAD4 exome AF: 0.641 AC: 122224 AN: 190622 Hom.: 39941 Cov.: 0 AF XY: 0.652 AC XY: 71973 AN XY: 110326

Gnomad4 AFR exome AF: 0.749

Gnomad4 AMR exome AF: 0.609

Gnomad4 ASJ exome AF: 0.556

Gnomad4 EAS exome AF: 0.743

Gnomad4 SAS exome AF: 0.732

Gnomad4 FIN exome AF: 0.630

Gnomad4 NFE exome AF: 0.612

Gnomad4 OTH exome AF: 0.639

GnomAD4 genome AF: 0.664 AC: 100832 AN: 151798 Hom.: 33928 Cov.: 30 AF XY: 0.669 AC XY: 49617 AN XY: 74188

Gnomad4 AFR AF: 0.755

Gnomad4 AMR AF: 0.649

Gnomad4 ASJ AF: 0.587

Gnomad4 EAS AF: 0.741

Gnomad4 SAS AF: 0.750

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.611

Gnomad4 OTH AF: 0.659

Alfa AF: 0.642 Hom.: 6076

Bravo AF: 0.667

Asia WGS AF: 0.773 AC: 2687 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.2
DANN	Benign	0.29

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs985937; hg19: chr6-100541187;