Variant 8-90060698-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_004929.4(CALB1):c.603C>T(p.Asp201=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000176 in 1,610,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00088 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

CALB1
NM_004929.4 splice_region, synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.68

Variant links:

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]

CALB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 8-90060698-G-A is Benign according to our data. Variant chr8-90060698-G-A is described in ClinVar as [Benign]. Clinvar id is 739023.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.68 with no splicing effect.

BS2

High AC in GnomAd4 at 134 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALB1	NM_004929.4 linkuse as main transcript	c.603C>T	p.Asp201=	splice_region_variant, synonymous_variant	10/11	ENST00000265431.7	NP_004920.1
CALB1	NM_001366795.1 linkuse as main transcript	c.528C>T	p.Asp176=	splice_region_variant, synonymous_variant	9/10		NP_001353724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALB1	ENST00000265431.7 linkuse as main transcript	c.603C>T	p.Asp201=	splice_region_variant, synonymous_variant	10/11	1	NM_004929.4	ENSP00000265431	P1	P05937-1
CALB1	ENST00000518457.5 linkuse as main transcript	c.432C>T	p.Asp144=	splice_region_variant, synonymous_variant	9/10	2		ENSP00000429602		P05937-2
CALB1	ENST00000469032.1 linkuse as main transcript	n.3644C>T		non_coding_transcript_exon_variant	2/3	2
CALB1	ENST00000497376.1 linkuse as main transcript	n.615C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.000855

AC:

130

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00302

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000215

AC:

AN:

251206

Hom.:

AF XY:

0.000162

AC XY:

AN XY:

135762

show subpopulations

Gnomad AFR exome

AF:

0.00295

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000102

AC:

149

AN:

1458554

Hom.:

Cov.:

AF XY:

0.0000840

AC XY:

AN XY:

725770

show subpopulations

Gnomad4 AFR exome

AF:

0.00278

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000352

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000880

AC:

134

AN:

152216

Hom.:

Cov.:

AF XY:

0.000954

AC XY:

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.00311

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000735

Hom.:

Bravo

AF:

0.000945

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 21, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

9.0

DANN

Benign

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over