7-128821040-C-T

Variant names:

• chr7-128821040-C-T
• rs3800560
• NM_022742.5:c.*6-759C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022742.5(CCDC136):​c.*6-759C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.093 in 152,178 control chromosomes in the GnomAD database, including 696 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 0.093 (696 hom., cov: 32)
• Consequence: CCDC136 NM_022742.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285
• Publications: 4 publications found

Genes affected

CCDC136 (HGNC:22225): (coiled-coil domain containing 136) Predicted to be involved in acrosome assembly and single fertilization. Predicted to be integral component of membrane. Predicted to be active in acrosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC136	NM_022742.5	c.*6-759C>T		intron_variant	Intron 17 of 17	ENST00000297788.9	NP_073579.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC136	ENST00000297788.9	c.*6-759C>T		intron_variant	Intron 17 of 17	1	NM_022742.5	ENSP00000297788.4

Frequencies

GnomAD3 genomes AF: 0.0930 AC: 14142 AN: 152056 Hom.: 696 Cov.: 32

Gnomad AFR AF: 0.0939

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0881

Gnomad ASJ AF: 0.0987

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.0852

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0865

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.0930 AC: 14153 AN: 152178 Hom.: 696 Cov.: 32 AF XY: 0.0932 AC XY: 6933 AN XY: 74404

African (AFR) AF: 0.0938 AC: 3894 AN: 41520

American (AMR) AF: 0.0880 AC: 1345 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0987 AC: 342 AN: 3466

East Asian (EAS) AF: 0.192 AC: 995 AN: 5180

South Asian (SAS) AF: 0.100 AC: 483 AN: 4824

European-Finnish (FIN) AF: 0.0852 AC: 901 AN: 10580

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0865 AC: 5883 AN: 68002

Other (OTH) AF: 0.106 AC: 225 AN: 2116

Alfa AF: 0.0978 Hom.: 252

Bravo AF: 0.0937

Asia WGS AF: 0.144 AC: 501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.7
DANN	Benign	0.67
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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: rs3800560; hg19: chr7-128461094;