rs6580

Positions:

• chr10-103447117-T-C

Variant summary

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

The NM_015916.5(CALHM2):​c.*35A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 1,546,426 control chromosomes in the GnomAD database, including 115,994 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 0.34 (9503 hom., cov: 33)
  • Exomes 𝑓: 0.39 (106491 hom.)
• Consequence: CALHM2 NM_015916.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

Genes affected

CALHM2 (HGNC:23493): (calcium homeostasis modulator family member 2) Predicted to enable cation channel activity. Involved in positive regulation of apoptotic process. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALHM2	NM_015916.5	c.*35A>G		3_prime_UTR_variant	4/4	ENST00000260743.10	NP_057000.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALHM2	ENST00000260743.10	c.*35A>G		3_prime_UTR_variant	4/4	1	NM_015916.5	ENSP00000260743	P1
CALHM2	ENST00000369788.7	c.*35A>G		3_prime_UTR_variant	4/4	2		ENSP00000358803	P1

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51757 AN: 152004 Hom.: 9497 Cov.: 33

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.348

GnomAD3 exomes AF: 0.382 AC: 80164 AN: 209942 Hom.: 15905 AF XY: 0.392 AC XY: 44033 AN XY: 112240

Gnomad AFR exome AF: 0.188

Gnomad AMR exome AF: 0.350

Gnomad ASJ exome AF: 0.352

Gnomad EAS exome AF: 0.347

Gnomad SAS exome AF: 0.506

Gnomad FIN exome AF: 0.447

Gnomad NFE exome AF: 0.390

Gnomad OTH exome AF: 0.391

GnomAD4 exome AF: 0.387 AC: 539887 AN: 1394304 Hom.: 106491 Cov.: 28 AF XY: 0.391 AC XY: 268682 AN XY: 687082

Gnomad4 AFR exome AF: 0.182

Gnomad4 AMR exome AF: 0.354

Gnomad4 ASJ exome AF: 0.355

Gnomad4 EAS exome AF: 0.353

Gnomad4 SAS exome AF: 0.504

Gnomad4 FIN exome AF: 0.441

Gnomad4 NFE exome AF: 0.386

Gnomad4 OTH exome AF: 0.380

GnomAD4 genome AF: 0.340 AC: 51786 AN: 152122 Hom.: 9503 Cov.: 33 AF XY: 0.346 AC XY: 25711 AN XY: 74348

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.358

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.357

Gnomad4 SAS AF: 0.497

Gnomad4 FIN AF: 0.454

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.348

Alfa AF: 0.383 Hom.: 16368

Bravo AF: 0.323

Asia WGS AF: 0.422 AC: 1465 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.5
DANN	Benign	0.60

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: rs6580; hg19: chr10-105206874; COSMIC: COSV53295314; COSMIC: COSV53295314;