ENST00000523716.5:c.-92-1143T>A

Variant names:

• chr8-90083245-A-T
• rs1800645
• ENST00000523716.5:c.-92-1143T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000523716.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALB1	ENST00000523716.5	TSL:2	c.-92-1143T>A		intron	N/A	ENSP00000429246.1
	CALB1	ENST00000520613.5	TSL:5	c.-92-1143T>A		intron	N/A	ENSP00000430281.1
	CALB1	ENST00000514406.2	TSL:5	c.-92-1143T>A		intron	N/A	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

African (AFR) AF: 0.794 AC: 32912 AN: 41432

American (AMR) AF: 0.713 AC: 10879 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.770 AC: 2671 AN: 3468

East Asian (EAS) AF: 0.609 AC: 3151 AN: 5172

South Asian (SAS) AF: 0.718 AC: 3450 AN: 4802

European-Finnish (FIN) AF: 0.693 AC: 7300 AN: 10528

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.730 AC: 49637 AN: 67964

Other (OTH) AF: 0.749 AC: 1577 AN: 2106

Alfa AF: 0.647 Hom.: 1811

Bravo AF: 0.747

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.19
DANN	Benign	0.40
PhyloP100		-0.79
PromoterAI		0.0096	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1800645; hg19: chr8-91095473;