7-128821040-C-T

Position:

• chr7-128821040-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CCDC136	NM_022742.5	c.*6-759C>T		intron_variant		ENST00000297788.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC136	ENST00000297788.9	c.*6-759C>T		intron_variant		1	NM_022742.5	A2

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

Gnomad4 AFR AF: 0.0938

Gnomad4 AMR AF: 0.0880

Gnomad4 ASJ AF: 0.0987

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.0852

Gnomad4 NFE AF: 0.0865

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0935 Hom.: 95

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

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: rs3800560; hg19: chr7-128461094;