7-51025175-G-A

Variant names:

• chr7-51025175-G-A
• rs76685455
• NM_015198.5:c.3702C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_015198.5(COBL):​c.3702C>T​(p.Thr1234Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00078 in 1,611,708 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0041 (4 hom., cov: 31)
  • Exomes 𝑓: 0.00044 (3 hom.)
• Consequence: COBL NM_015198.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.76
• 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 7-51025175-G-A is Benign according to our data. Variant chr7-51025175-G-A is described in ClinVar as Benign. ClinVar VariationId is 726860.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.76 with no splicing effect.
• 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.3702C>T	p.Thr1234Thr	synonymous	Exon 12 of 13	NP_056013.2
	COBL	NM_001410881.1		c.3948C>T	p.Thr1316Thr	synonymous	Exon 14 of 15	NP_001397810.1	O75128-2
	COBL	NM_001287436.3		c.3732C>T	p.Thr1244Thr	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.3702C>T	p.Thr1234Thr	synonymous	Exon 12 of 13	ENSP00000265136.7	O75128-1
	COBL	ENST00000431948.6	TSL:1	c.3948C>T	p.Thr1316Thr	synonymous	Exon 14 of 15	ENSP00000413498.2	O75128-2
	COBL	ENST00000395542.6	TSL:1	c.3732C>T	p.Thr1244Thr	synonymous	Exon 13 of 14	ENSP00000378912.3	O75128-7

Frequencies

GnomAD3 genomes AF: 0.00405 AC: 615 AN: 151888 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00269

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.000986 AC: 246 AN: 249488 AF XY: 0.000749

Gnomad AFR exome AF: 0.0134

Gnomad AMR exome AF: 0.000636

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000268

Gnomad OTH exome AF: 0.000491

GnomAD4 exome AF: 0.000438 AC: 640 AN: 1459704 Hom.: 3 Cov.: 38 AF XY: 0.000353 AC XY: 256 AN XY: 726168

African (AFR) AF: 0.0156 AC: 521 AN: 33406

American (AMR) AF: 0.000895 AC: 40 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

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

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86166

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4142

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1111834

Other (OTH) AF: 0.000880 AC: 53 AN: 60212

GnomAD4 genome AF: 0.00406 AC: 617 AN: 152004 Hom.: 4 Cov.: 31 AF XY: 0.00417 AC XY: 310 AN XY: 74308

African (AFR) AF: 0.0136 AC: 563 AN: 41438

American (AMR) AF: 0.00268 AC: 41 AN: 15284

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

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5142

South Asian (SAS) AF: 0.00 AC: 0 AN: 4792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67962

Other (OTH) AF: 0.00332 AC: 7 AN: 2110

Alfa AF: 0.00135 Hom.: 0

Bravo AF: 0.00496

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	-0.87
CADD	Benign	0.089
DANN	Benign	0.73
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs76685455; hg19: chr7-51092872;