10-103455175-T-C

Position:

• chr10-103455175-T-C

Variant summary

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

The NM_001001412.4(CALHM1):​c.*87A>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 0.338 in 1,471,828 control chromosomes in the GnomAD database, including 85,278 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 0.35 (9534 hom., cov: 33)
  • Exomes 𝑓: 0.34 (75744 hom.)
• Consequence: CALHM1 NM_001001412.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.787

Genes affected

CALHM1 (HGNC:23494): (calcium homeostasis modulator 1) This gene encodes a calcium channel that plays a role in processing of amyloid-beta precursor protein. A polymorphism at this locus has been reported to be associated with susceptibility to late-onset Alzheimer's disease in some populations, but the pathogenicity of this polymorphism is unclear.[provided by RefSeq, Mar 2010]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALHM1	NM_001001412.4	c.*87A>G		3_prime_UTR_variant	2/2	ENST00000329905.6
LOC124902494	XR_007062275.1	n.794+1939T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALHM1	ENST00000329905.6	c.*87A>G		3_prime_UTR_variant	2/2	1	NM_001001412.4	P1
	ENST00000411906.1	n.391+1939T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53312 AN: 151786 Hom.: 9516 Cov.: 33

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.330

GnomAD4 exome AF: 0.336 AC: 444117 AN: 1319924 Hom.: 75744 Cov.: 29 AF XY: 0.334 AC XY: 214883 AN XY: 643796

Gnomad4 AFR exome AF: 0.404

Gnomad4 AMR exome AF: 0.437

Gnomad4 ASJ exome AF: 0.308

Gnomad4 EAS exome AF: 0.473

Gnomad4 SAS exome AF: 0.280

Gnomad4 FIN exome AF: 0.303

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 0.335

GnomAD4 genome AF: 0.351 AC: 53372 AN: 151904 Hom.: 9534 Cov.: 33 AF XY: 0.351 AC XY: 26083 AN XY: 74272

Gnomad4 AFR AF: 0.402

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.332

Alfa AF: 0.333 Hom.: 6729

Bravo AF: 0.364

Asia WGS AF: 0.380 AC: 1326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.59

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: rs729211; hg19: chr10-105214932; COSMIC: COSV53295867; COSMIC: COSV53295867;