ENST00000545005.5:c.-24+91G>A

Variant names:

• chr1-169459706-C-T
• rs1208134
• ENST00000545005.5:c.-24+91G>A

Variant summary

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

The ENST00000545005.5(CCDC181):​c.-24+91G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.93 in 151,890 control chromosomes in the GnomAD database, including 65,740 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 0.93 (65737 hom., cov: 27)
  • Exomes 𝑓: 0.88 (3 hom.)
• Consequence: CCDC181 ENST00000545005.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 8 publications found

Genes affected

CCDC181 (HGNC:28051): (coiled-coil domain containing 181) Predicted to enable microtubule binding activity. Predicted to be located in manchette and sperm flagellum. [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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000545005.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC181	NM_001300968.1		c.-24+91G>A		intron	N/A	NP_001287897.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC181	ENST00000545005.5	TSL:1	c.-24+91G>A		intron	N/A	ENSP00000442297.1
	CCDC181	ENST00000445428.5	TSL:1	n.268+91G>A		intron	N/A
	CCDC181	ENST00000437857.2	TSL:3	n.237+91G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.930 AC: 141168 AN: 151766 Hom.: 65674 Cov.: 27

Gnomad AFR AF: 0.921

Gnomad AMI AF: 0.973

Gnomad AMR AF: 0.934

Gnomad ASJ AF: 0.954

Gnomad EAS AF: 0.938

Gnomad SAS AF: 0.894

Gnomad FIN AF: 0.938

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.934

Gnomad OTH AF: 0.937

GnomAD4 exome AF: 0.875 AC: 7 AN: 8 Hom.: 3 AF XY: 0.875 AC XY: 7 AN XY: 8

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.833 AC: 5 AN: 6

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.930 AC: 141290 AN: 151882 Hom.: 65737 Cov.: 27 AF XY: 0.930 AC XY: 69058 AN XY: 74224

African (AFR) AF: 0.921 AC: 38125 AN: 41394

American (AMR) AF: 0.934 AC: 14241 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.954 AC: 3312 AN: 3472

East Asian (EAS) AF: 0.938 AC: 4821 AN: 5138

South Asian (SAS) AF: 0.895 AC: 4296 AN: 4800

European-Finnish (FIN) AF: 0.938 AC: 9880 AN: 10534

Middle Eastern (MID) AF: 0.908 AC: 267 AN: 294

European-Non Finnish (NFE) AF: 0.934 AC: 63491 AN: 67982

Other (OTH) AF: 0.937 AC: 1970 AN: 2102

Alfa AF: 0.933 Hom.: 122059

Bravo AF: 0.931

Asia WGS AF: 0.902 AC: 3140 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.28
DANN	Benign	0.50
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1208134; hg19: chr1-169428944;