rs6470671

Variant names:

• chr8-90085370-G-T
• rs6470671
• ENST00000523716.5:c.-92-3268C>A

Variant summary

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

The ENST00000523716.5(CALB1):​c.-92-3268C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 151,908 control chromosomes in the GnomAD database, including 44,216 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 0.76 (44216 hom., cov: 31)
• Consequence: CALB1 ENST00000523716.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0750

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALB1	ENST00000523716.5	c.-92-3268C>A		intron_variant	Intron 1 of 7	2		ENSP00000429246.1
CALB1	ENST00000520613.5	c.-92-3268C>A		intron_variant	Intron 2 of 7	5		ENSP00000430281.1
CALB1	ENST00000514406.2	c.-92-3268C>A		intron_variant	Intron 2 of 3	5		ENSP00000430192.1

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115344 AN: 151790 Hom.: 44181 Cov.: 31

Gnomad AFR AF: 0.859

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.723

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.761

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

GnomAD4 genome AF: 0.760 AC: 115434 AN: 151908 Hom.: 44216 Cov.: 31 AF XY: 0.755 AC XY: 56065 AN XY: 74270

Gnomad4 AFR AF: 0.859

Gnomad4 AMR AF: 0.723

Gnomad4 ASJ AF: 0.775

Gnomad4 EAS AF: 0.611

Gnomad4 SAS AF: 0.719

Gnomad4 FIN AF: 0.695

Gnomad4 NFE AF: 0.731

Gnomad4 OTH AF: 0.762

Alfa AF: 0.748 Hom.: 5322

Bravo AF: 0.768

Asia WGS AF: 0.695 AC: 2412 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.42
DANN	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6470671; hg19: chr8-91097598;