8-90077622-T-C

Variant names:

• chr8-90077622-T-C
• rs6470668
• NM_004929.4:c.231+751A>G

Variant summary

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

The NM_004929.4(CALB1):​c.231+751A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 151,946 control chromosomes in the GnomAD database, including 42,803 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 (42803 hom., cov: 32)
• Consequence: CALB1 NM_004929.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.474
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004929.4. 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
	CALB1	NM_004929.4	MANE Select	c.231+751A>G		intron	N/A	NP_004920.1	P05937-1
	CALB1	NM_001366795.1		c.156+4404A>G		intron	N/A	NP_001353724.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALB1	ENST00000265431.7	TSL:1 MANE Select	c.231+751A>G		intron	N/A	ENSP00000265431.3	P05937-1
	CALB1	ENST00000920117.1		c.231+751A>G		intron	N/A	ENSP00000590176.1
	CALB1	ENST00000892430.1		c.156+4404A>G		intron	N/A	ENSP00000562489.1

Frequencies

GnomAD3 genomes AF: 0.748 AC: 113636 AN: 151828 Hom.: 42762 Cov.: 32

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.772

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.755

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

GnomAD4 genome AF: 0.749 AC: 113734 AN: 151946 Hom.: 42803 Cov.: 32 AF XY: 0.744 AC XY: 55269 AN XY: 74282

African (AFR) AF: 0.820 AC: 34031 AN: 41504

American (AMR) AF: 0.719 AC: 10976 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.772 AC: 2676 AN: 3468

East Asian (EAS) AF: 0.612 AC: 3158 AN: 5164

South Asian (SAS) AF: 0.718 AC: 3470 AN: 4830

European-Finnish (FIN) AF: 0.694 AC: 7328 AN: 10562

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.731 AC: 49565 AN: 67840

Other (OTH) AF: 0.756 AC: 1598 AN: 2114

Alfa AF: 0.735 Hom.: 20594

Bravo AF: 0.755

Asia WGS AF: 0.694 AC: 2414 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.44
DANN	Benign	0.39
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs6470668; hg19: chr8-91089850;