rs11191692

Positions:

• chr10-103454008-G-A
• chr10-103454008-G-C

Variant summary

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

The NM_001001412.4(CALHM1):​c.*1254C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,122 control chromosomes in the GnomAD database, including 7,738 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 0.29 (7737 hom., cov: 32)
  • Exomes 𝑓: 0.38 (1 hom.)
• Consequence: CALHM1 NM_001001412.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.248

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]

ENSG00000234699 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALHM1	NM_001001412.4	c.*1254C>T		3_prime_UTR_variant	2/2	ENST00000329905.6	NP_001001412.3
LOC124902494	XR_007062275.1	n.794+772G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALHM1	ENST00000329905	c.*1254C>T		3_prime_UTR_variant	2/2	1	NM_001001412.4	ENSP00000329926.6
ENSG00000234699	ENST00000411906.1	n.391+772G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44544 AN: 151988 Hom.: 7729 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.302

GnomAD4 exome AF: 0.375 AC: 6 AN: 16 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 4 AN XY: 8

Gnomad4 FIN exome AF: 0.625

Gnomad4 NFE exome AF: 0.125

GnomAD4 genome AF: 0.293 AC: 44568 AN: 152106 Hom.: 7737 Cov.: 32 AF XY: 0.299 AC XY: 22220 AN XY: 74346

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.441

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.302

Alfa AF: 0.355 Hom.: 13328

Bravo AF: 0.271

Asia WGS AF: 0.367 AC: 1274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.63

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: rs11191692; hg19: chr10-105213765;