chr11-67519197-T-C

Variant names:

• chr11-67519197-T-C
• rs73506069
• NM_016366.3:c.638-33A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016366.3(CABP2):​c.638-33A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00814 in 1,613,232 control chromosomes in the GnomAD database, including 754 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (392 hom., cov: 32)
  • Exomes 𝑓: 0.0048 (362 hom.)
• Consequence: CABP2 NM_016366.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0420
• Publications: 5 publications found

Genes affected

CABP2 (HGNC:1385): (calcium binding protein 2) This gene belongs to a subfamily of calcium binding proteins that share similarity to calmodulin. Like calmodulin, these family members can likely stimulate calmodulin-dependent kinase II and the protein phosphatase calcineurin. Calcium binding proteins are an important component of calcium mediated cellular signal transduction. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

CABP2 Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive nonsyndromic hearing loss 93

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 11-67519197-T-C is Benign according to our data. Variant chr11-67519197-T-C is described in ClinVar as Benign. ClinVar VariationId is 1272043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016366.3. 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
	CABP2	NM_016366.3	MANE Select	c.638-33A>G		intron	N/A	NP_057450.2	Q9NPB3-1
	CABP2	NM_001318496.2		c.656-33A>G		intron	N/A	NP_001305425.1	F1T0K2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CABP2	ENST00000294288.5	TSL:1 MANE Select	c.638-33A>G		intron	N/A	ENSP00000294288.4	Q9NPB3-1
	CABP2	ENST00000545205.2	TSL:1	n.*423-33A>G		intron	N/A	ENSP00000446180.1	F5H458
	CABP2	ENST00000636477.1	TSL:5	c.590-33A>G		intron	N/A	ENSP00000490746.1	A0A1B0GW24

Frequencies

GnomAD3 genomes AF: 0.0407 AC: 6184 AN: 151828 Hom.: 393 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0206

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.00150

Gnomad OTH AF: 0.0336

GnomAD2 exomes AF: 0.0110 AC: 2766 AN: 250508 AF XY: 0.00833

Gnomad AFR exome AF: 0.138

Gnomad AMR exome AF: 0.00882

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00133

Gnomad OTH exome AF: 0.00848

GnomAD4 exome AF: 0.00475 AC: 6946 AN: 1461286 Hom.: 362 Cov.: 30 AF XY: 0.00421 AC XY: 3062 AN XY: 726972

African (AFR) AF: 0.136 AC: 4543 AN: 33430

American (AMR) AF: 0.0104 AC: 467 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.000475 AC: 41 AN: 86242

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53416

Middle Eastern (MID) AF: 0.0142 AC: 82 AN: 5768

European-Non Finnish (NFE) AF: 0.00102 AC: 1139 AN: 1111518

Other (OTH) AF: 0.0111 AC: 668 AN: 60362

GnomAD4 genome AF: 0.0408 AC: 6193 AN: 151946 Hom.: 392 Cov.: 32 AF XY: 0.0392 AC XY: 2913 AN XY: 74262

African (AFR) AF: 0.137 AC: 5689 AN: 41392

American (AMR) AF: 0.0205 AC: 312 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.000831 AC: 4 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.00150 AC: 102 AN: 67986

Other (OTH) AF: 0.0332 AC: 70 AN: 2106

Alfa AF: 0.0159 Hom.: 63

Bravo AF: 0.0465

Asia WGS AF: 0.00693 AC: 25 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	11
DANN	Benign	0.54
PhyloP100		0.042
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs73506069; hg19: chr11-67286668;