rs1805874

chr8-90069834-A-Cchr8-90069834-A-T

Variant summary

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

The NM_004929.4(CALB1):c.232-597T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 152,000 control chromosomes in the GnomAD database, including 33,613 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 0.66 (33613 hom., cov: 31)
• Consequence: CALB1 NM_004929.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALB1	NM_004929.4	c.232-597T>G		intron_variant		ENST00000265431.7
CALB1	NM_001366795.1	c.157-597T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALB1	ENST00000265431.7	c.232-597T>G		intron_variant		1	NM_004929.4	P1

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99826 AN: 151884 Hom.: 33603 Cov.: 31

Gnomad AFR AF: 0.742

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.657 AC: 99880 AN: 152000 Hom.: 33613 Cov.: 31 AF XY: 0.646 AC XY: 47961 AN XY: 74288

Gnomad4 AFR AF: 0.742

Gnomad4 AMR AF: 0.531

Gnomad4 ASJ AF: 0.709

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.535

Gnomad4 FIN AF: 0.595

Gnomad4 NFE AF: 0.675

Gnomad4 OTH AF: 0.651

Alfa AF: 0.664 Hom.: 30922

Bravo AF: 0.655

Asia WGS AF: 0.416 AC: 1450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	5.1
Dann	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1805874; hg19: chr8-91082062;