8-90083245-A-T

Position:

• chr8-90083245-A-T

Variant summary

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

The ENST00000523716.5(CALB1):​c.-92-1143T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 151,938 control chromosomes in the GnomAD database, including 41,814 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 0.74 (41814 hom., cov: 30)
• Consequence: CALB1 ENST00000523716.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.785

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.90083245A>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALB1	ENST00000523716.5	c.-92-1143T>A		intron_variant		2		ENSP00000429246.1
CALB1	ENST00000520613.5	c.-92-1143T>A		intron_variant		5		ENSP00000430281.1
CALB1	ENST00000514406.2	c.-92-1143T>A		intron_variant		5		ENSP00000430192.1

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112425 AN: 151820 Hom.: 41787 Cov.: 30

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.730

Gnomad OTH AF: 0.751

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

GnomAD4 genome AF: 0.740 AC: 112504 AN: 151938 Hom.: 41814 Cov.: 30 AF XY: 0.736 AC XY: 54655 AN XY: 74270

Gnomad4 AFR AF: 0.794

Gnomad4 AMR AF: 0.713

Gnomad4 ASJ AF: 0.770

Gnomad4 EAS AF: 0.609

Gnomad4 SAS AF: 0.718

Gnomad4 FIN AF: 0.693

Gnomad4 NFE AF: 0.730

Gnomad4 OTH AF: 0.749

Alfa AF: 0.647 Hom.: 1811

Bravo AF: 0.747

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.19
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1800645; hg19: chr8-91095473;