rs7815279

Positions:

• chr8-90081858-A-C
• chr8-90081858-A-G
• chr8-90081858-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.156+168T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 150,142 control chromosomes in the GnomAD database, including 41,664 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 0.75 (41664 hom., cov: 27)
• Consequence: CALB1 NM_004929.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALB1	NM_004929.4	c.156+168T>G		intron_variant		ENST00000265431.7	NP_004920.1
CALB1	NM_001366795.1	c.156+168T>G		intron_variant			NP_001353724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALB1	ENST00000265431.7	c.156+168T>G		intron_variant		1	NM_004929.4	ENSP00000265431	P1

Frequencies

GnomAD3 genomes AF: 0.747 AC: 112021 AN: 150028 Hom.: 41634 Cov.: 27

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.723

Gnomad ASJ AF: 0.772

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.734

Gnomad OTH AF: 0.757

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

GnomAD4 genome AF: 0.747 AC: 112104 AN: 150142 Hom.: 41664 Cov.: 27 AF XY: 0.744 AC XY: 54402 AN XY: 73132

Gnomad4 AFR AF: 0.800

Gnomad4 AMR AF: 0.723

Gnomad4 ASJ AF: 0.772

Gnomad4 EAS AF: 0.620

Gnomad4 SAS AF: 0.724

Gnomad4 FIN AF: 0.714

Gnomad4 NFE AF: 0.734

Gnomad4 OTH AF: 0.758

Alfa AF: 0.731 Hom.: 68208

Bravo AF: 0.747

Asia WGS AF: 0.692 AC: 2407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.89
DANN	Benign	0.50

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: rs7815279; hg19: chr8-91094086; COSMIC: COSV55368091; COSMIC: COSV55368091;