7-51051656-C-T

Position:

• chr7-51051656-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015198.5(COBL):​c.1097-7964G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 152,026 control chromosomes in the GnomAD database, including 16,490 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 0.41 (16490 hom., cov: 33)
• Consequence: COBL NM_015198.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.82

Genes affected

COBL (HGNC:22199): (cordon-bleu WH2 repeat protein) This gene encodes a protein that contains WH2 domains (WASP, Wiskott-Aldrich syndrome protein, homology domain-2) that interact with actin. The encoded actin regulator protein is required for growth and assembly of brush border microvilli that play a role in maintaining intestinal homeostasis. A similar protein in mouse functions in midbrain neural tube closure. A pseudogene of this gene is located on chromosome X. [provided by RefSeq, Oct 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COBL	NM_015198.5	c.1097-7964G>A		intron_variant		ENST00000265136.12	NP_056013.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COBL	ENST00000265136.12	c.1097-7964G>A		intron_variant		1	NM_015198.5	ENSP00000265136	P2

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61896 AN: 151908 Hom.: 16437 Cov.: 33

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.408 AC: 62014 AN: 152026 Hom.: 16490 Cov.: 33 AF XY: 0.411 AC XY: 30512 AN XY: 74314

Gnomad4 AFR AF: 0.749

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.389

Alfa AF: 0.262 Hom.: 6040

Bravo AF: 0.435

Asia WGS AF: 0.522 AC: 1812 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0080
DANN	Benign	0.64

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

Other links and lift over

dbSNP: rs10248051; hg19: chr7-51119353;