chr7-51025148-G-A

Variant names:

• chr7-51025148-G-A
• rs146319427
• NM_015198.5:c.3729C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_015198.5(COBL):​c.3729C>T​(p.Asp1243Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00301 in 1,611,598 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0048 (4 hom., cov: 31)
  • Exomes 𝑓: 0.0028 (24 hom.)
• Consequence: COBL NM_015198.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.03
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 7-51025148-G-A is Benign according to our data. Variant chr7-51025148-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2657504.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.03 with no splicing effect.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00283 (4133/1459662) while in subpopulation MID AF = 0.0239 (99/4144). AF 95% confidence interval is 0.0201. There are 24 homozygotes in GnomAdExome4. There are 2057 alleles in the male GnomAdExome4 subpopulation. Median coverage is 36. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015198.5. 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
	COBL	NM_015198.5	MANE Select	c.3729C>T	p.Asp1243Asp	synonymous	Exon 12 of 13	NP_056013.2
	COBL	NM_001410881.1		c.3975C>T	p.Asp1325Asp	synonymous	Exon 14 of 15	NP_001397810.1	O75128-2
	COBL	NM_001287436.3		c.3759C>T	p.Asp1253Asp	synonymous	Exon 13 of 14	NP_001274365.1	O75128-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COBL	ENST00000265136.12	TSL:1 MANE Select	c.3729C>T	p.Asp1243Asp	synonymous	Exon 12 of 13	ENSP00000265136.7	O75128-1
	COBL	ENST00000431948.6	TSL:1	c.3975C>T	p.Asp1325Asp	synonymous	Exon 14 of 15	ENSP00000413498.2	O75128-2
	COBL	ENST00000395542.6	TSL:1	c.3759C>T	p.Asp1253Asp	synonymous	Exon 13 of 14	ENSP00000378912.3	O75128-7

Frequencies

GnomAD3 genomes AF: 0.00479 AC: 727 AN: 151816 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.00680

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00956

Gnomad ASJ AF: 0.0283

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.00208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00234

Gnomad OTH AF: 0.00959

GnomAD2 exomes AF: 0.00427 AC: 1064 AN: 249078 AF XY: 0.00419

Gnomad AFR exome AF: 0.00683

Gnomad AMR exome AF: 0.00650

Gnomad ASJ exome AF: 0.0285

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00260

Gnomad OTH exome AF: 0.00900

GnomAD4 exome AF: 0.00283 AC: 4133 AN: 1459662 Hom.: 24 Cov.: 36 AF XY: 0.00283 AC XY: 2057 AN XY: 726148

African (AFR) AF: 0.00709 AC: 237 AN: 33406

American (AMR) AF: 0.00718 AC: 321 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.0288 AC: 752 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00299 AC: 258 AN: 86164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.0239 AC: 99 AN: 4144

European-Non Finnish (NFE) AF: 0.00186 AC: 2072 AN: 1111808

Other (OTH) AF: 0.00654 AC: 394 AN: 60208

GnomAD4 genome AF: 0.00477 AC: 725 AN: 151936 Hom.: 4 Cov.: 31 AF XY: 0.00485 AC XY: 360 AN XY: 74244

African (AFR) AF: 0.00673 AC: 279 AN: 41466

American (AMR) AF: 0.00955 AC: 146 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0283 AC: 98 AN: 3468

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5128

South Asian (SAS) AF: 0.00209 AC: 10 AN: 4796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10526

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.00234 AC: 159 AN: 67950

Other (OTH) AF: 0.00949 AC: 20 AN: 2108

Alfa AF: 0.00549 Hom.: 4

Bravo AF: 0.00559

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	1.2
DANN	Benign	0.92
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs146319427; hg19: chr7-51092845; COSMIC: COSV104371332;