rs16902897

Positions:

• chr8-90083369-A-G
• chr8-90083369-A-T

Variant summary

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

The ENST00000523716.5(CALB1):​c.-92-1267T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0499 in 152,156 control chromosomes in the GnomAD database, including 259 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 0.050 (259 hom., cov: 31)
• Consequence: CALB1 ENST00000523716.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.576

Genes affected

CALB1 (HGNC:1434): (calbindin 1) The protein encoded by this gene is a member of the calcium-binding protein superfamily that includes calmodulin and troponin C. Originally described as a 27 kDa protein, it is now known to be a 28 kDa protein. It contains four active calcium-binding domains, and has two modified domains that are thought to have lost their calcium binding capability. This protein is thought to buffer entry of calcium upon stimulation of glutamate receptors. Depletion of this protein was noted in patients with Huntington disease. [provided by RefSeq, Jan 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALB1	ENST00000514406.2	c.-92-1267T>C		intron_variant		5		ENSP00000430192
CALB1	ENST00000520613.5	c.-92-1267T>C		intron_variant		5		ENSP00000430281
CALB1	ENST00000523716.5	c.-92-1267T>C		intron_variant		2		ENSP00000429246

Frequencies

GnomAD3 genomes AF: 0.0498 AC: 7577 AN: 152038 Hom.: 255 Cov.: 31

Gnomad AFR AF: 0.0675

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0763

Gnomad ASJ AF: 0.0499

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.0719

Gnomad FIN AF: 0.0388

Gnomad MID AF: 0.0255

Gnomad NFE AF: 0.0297

Gnomad OTH AF: 0.0589

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0499 AC: 7600 AN: 152156 Hom.: 259 Cov.: 31 AF XY: 0.0514 AC XY: 3826 AN XY: 74392

Gnomad4 AFR AF: 0.0675

Gnomad4 AMR AF: 0.0762

Gnomad4 ASJ AF: 0.0499

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.0732

Gnomad4 FIN AF: 0.0388

Gnomad4 NFE AF: 0.0297

Gnomad4 OTH AF: 0.0649

Alfa AF: 0.0327 Hom.: 41

Bravo AF: 0.0552

Asia WGS AF: 0.122 AC: 424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.93
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16902897; hg19: chr8-91095597;