NM_015916.5:c.*35A>G

Variant names:

• chr10-103447117-T-C
• rs6580
• NM_015916.5:c.*35A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 32 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015916.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALHM2	NM_015916.5	MANE Select	c.*35A>G		3_prime_UTR	Exon 4 of 4	NP_057000.2
	CALHM2	NR_024552.2		n.1467A>G		non_coding_transcript_exon	Exon 4 of 4
	CALHM2	NR_046344.2		n.1480A>G		non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALHM2	ENST00000260743.10	TSL:1 MANE Select	c.*35A>G		3_prime_UTR	Exon 4 of 4	ENSP00000260743.5
	CALHM2	ENST00000369788.7	TSL:2	c.*35A>G		3_prime_UTR	Exon 4 of 4	ENSP00000358803.3

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

GnomAD2 exomes AF: 0.382 AC: 80164 AN: 209942 AF XY: 0.392

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 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

African (AFR) AF: 0.182 AC: 5740 AN: 31522

American (AMR) AF: 0.354 AC: 13003 AN: 36768

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 7854 AN: 22138

East Asian (EAS) AF: 0.353 AC: 13761 AN: 38970

South Asian (SAS) AF: 0.504 AC: 38684 AN: 76800

European-Finnish (FIN) AF: 0.441 AC: 22635 AN: 51284

Middle Eastern (MID) AF: 0.335 AC: 1811 AN: 5414

European-Non Finnish (NFE) AF: 0.386 AC: 414560 AN: 1073948

Other (OTH) AF: 0.380 AC: 21839 AN: 57460

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

African (AFR) AF: 0.195 AC: 8116 AN: 41536

American (AMR) AF: 0.358 AC: 5479 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1215 AN: 3472

East Asian (EAS) AF: 0.357 AC: 1843 AN: 5166

South Asian (SAS) AF: 0.497 AC: 2393 AN: 4818

European-Finnish (FIN) AF: 0.454 AC: 4794 AN: 10560

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26788 AN: 67968

Other (OTH) AF: 0.348 AC: 734 AN: 2110

Alfa AF: 0.376 Hom.: 19762

Bravo AF: 0.323

Asia WGS AF: 0.422 AC: 1465 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.5
DANN	Benign	0.60
PhyloP100		-1.3
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: rs6580; hg19: chr10-105206874; COSMIC: COSV53295314; COSMIC: COSV53295314;