8-90085478-C-T

Variant names:

• chr8-90085478-C-T
• rs7459577
• ENST00000523716.5:c.-92-3376G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000523716.5(CALB1):​c.-92-3376G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 151,876 control chromosomes in the GnomAD database, including 41,847 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 (41847 hom., cov: 31)
• Consequence: CALB1 ENST00000523716.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• Publications: 2 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=-0.94).
• 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

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

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALB1	ENST00000523716.5	TSL:2	c.-92-3376G>A		intron	N/A	ENSP00000429246.1	E5RIZ8
	CALB1	ENST00000520613.5	TSL:5	c.-92-3376G>A		intron	N/A	ENSP00000430281.1	E5RG14
	CALB1	ENST00000514406.2	TSL:5	c.-92-3376G>A		intron	N/A	ENSP00000430192.1

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112455 AN: 151758 Hom.: 41815 Cov.: 31

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.758

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.751

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

GnomAD4 genome AF: 0.741 AC: 112541 AN: 151876 Hom.: 41847 Cov.: 31 AF XY: 0.737 AC XY: 54661 AN XY: 74210

African (AFR) AF: 0.794 AC: 32902 AN: 41416

American (AMR) AF: 0.713 AC: 10891 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 2689 AN: 3468

East Asian (EAS) AF: 0.611 AC: 3155 AN: 5164

South Asian (SAS) AF: 0.719 AC: 3469 AN: 4824

European-Finnish (FIN) AF: 0.696 AC: 7308 AN: 10504

Middle Eastern (MID) AF: 0.750 AC: 219 AN: 292

European-Non Finnish (NFE) AF: 0.731 AC: 49616 AN: 67918

Other (OTH) AF: 0.752 AC: 1584 AN: 2106

Alfa AF: 0.723 Hom.: 16601

Bravo AF: 0.747

Asia WGS AF: 0.690 AC: 2386 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.9
DANN	Benign	0.45
PhyloP100		0.31

Splicing

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

Other links and lift over

dbSNP: rs7459577; hg19: chr8-91097706;