rs1805874

Variant names:

• chr8-90069834-A-C
• rs1805874
• NM_004929.4:c.232-597T>G

Your query was ambiguous. Multiple possible variants found:

• chr8-90069834-A-C
• chr8-90069834-A-T

Variant summary

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

The NM_004929.4(CALB1):​c.232-597T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 152,000 control chromosomes in the GnomAD database, including 33,613 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 0.66 (33613 hom., cov: 31)
• Consequence: CALB1 NM_004929.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57
• Publications: 11 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.735 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.232-597T>G		intron	N/A	NP_004920.1	P05937-1
	CALB1	NM_001366795.1		c.157-597T>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.232-597T>G		intron	N/A	ENSP00000265431.3	P05937-1
	CALB1	ENST00000920117.1		c.232-597T>G		intron	N/A	ENSP00000590176.1
	CALB1	ENST00000892430.1		c.157-597T>G		intron	N/A	ENSP00000562489.1

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99826 AN: 151884 Hom.: 33603 Cov.: 31

Gnomad AFR AF: 0.742

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.657 AC: 99880 AN: 152000 Hom.: 33613 Cov.: 31 AF XY: 0.646 AC XY: 47961 AN XY: 74288

African (AFR) AF: 0.742 AC: 30734 AN: 41444

American (AMR) AF: 0.531 AC: 8103 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 2462 AN: 3472

East Asian (EAS) AF: 0.306 AC: 1578 AN: 5158

South Asian (SAS) AF: 0.535 AC: 2577 AN: 4814

European-Finnish (FIN) AF: 0.595 AC: 6286 AN: 10560

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.675 AC: 45870 AN: 67964

Other (OTH) AF: 0.651 AC: 1372 AN: 2108

Alfa AF: 0.665 Hom.: 41406

Bravo AF: 0.655

Asia WGS AF: 0.416 AC: 1450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.1
DANN	Benign	0.49
PhyloP100		1.6
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: rs1805874; hg19: chr8-91082062;