rs59197085

Positions:

• chr7-128820702-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022742.5(CCDC136):​c.*6-1097G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 152,190 control chromosomes in the GnomAD database, including 832 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 0.10 (832 hom., cov: 32)
• Consequence: CCDC136 NM_022742.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC136	NM_022742.5	c.*6-1097G>A		intron_variant		ENST00000297788.9	NP_073579.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC136	ENST00000297788.9	c.*6-1097G>A		intron_variant		1	NM_022742.5	ENSP00000297788	A2

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15207 AN: 152072 Hom.: 829 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0907

Gnomad ASJ AF: 0.0991

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0849

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0865

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.100 AC: 15236 AN: 152190 Hom.: 832 Cov.: 32 AF XY: 0.100 AC XY: 7453 AN XY: 74406

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.0906

Gnomad4 ASJ AF: 0.0991

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.0849

Gnomad4 NFE AF: 0.0866

Gnomad4 OTH AF: 0.111

Alfa AF: 0.0957 Hom.: 90

Bravo AF: 0.102

Asia WGS AF: 0.148 AC: 515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.4
DANN	Benign	0.77

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: rs59197085; hg19: chr7-128460756; COSMIC: COSV52798942; COSMIC: COSV52798942;