7-51025175-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_015198.5(COBL):​c.3702C>A​(p.Thr1234Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T1234T) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: COBL NM_015198.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.76
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP7: Synonymous conserved (PhyloP=-2.76 with no splicing effect.

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>A	p.Thr1234Thr	synonymous	Exon 12 of 13	NP_056013.2
	COBL	NM_001410881.1		c.3948C>A	p.Thr1316Thr	synonymous	Exon 14 of 15	NP_001397810.1	O75128-2
	COBL	NM_001287436.3		c.3732C>A	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>A	p.Thr1234Thr	synonymous	Exon 12 of 13	ENSP00000265136.7	O75128-1
	COBL	ENST00000431948.6	TSL:1	c.3948C>A	p.Thr1316Thr	synonymous	Exon 14 of 15	ENSP00000413498.2	O75128-2
	COBL	ENST00000395542.6	TSL:1	c.3732C>A	p.Thr1244Thr	synonymous	Exon 13 of 14	ENSP00000378912.3	O75128-7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459704 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 726168

African (AFR) AF: 0.00 AC: 0 AN: 33406

American (AMR) AF: 0.00 AC: 0 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: 0.00 AC: 0 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: 8.99e-7 AC: 1 AN: 1111834

Other (OTH) AF: 0.00 AC: 0 AN: 60212

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.010
DANN	Benign	0.61
PhyloP100		-2.8

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;