chr12-28416781-T-C

Position:

• chr12-28416781-T-C

Variant summary

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

The NM_018318.5(CCDC91):​c.762+25370T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,004 control chromosomes in the GnomAD database, including 4,336 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 0.22 (4336 hom., cov: 31)
• Consequence: CCDC91 NM_018318.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

Genes affected

CCDC91 (HGNC:24855): (coiled-coil domain containing 91) Predicted to enable identical protein binding activity. Involved in Golgi to lysosome transport. Located in nucleoplasm and trans-Golgi network. [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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC91	NM_018318.5	c.762+25370T>C		intron_variant		ENST00000536442.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC91	ENST00000536442.6	c.762+25370T>C		intron_variant		5	NM_018318.5	P1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33066 AN: 151886 Hom.: 4334 Cov.: 31

Gnomad AFR AF: 0.0977

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.0467

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.218 AC: 33079 AN: 152004 Hom.: 4336 Cov.: 31 AF XY: 0.213 AC XY: 15795 AN XY: 74266

Gnomad4 AFR AF: 0.0977

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.0470

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.218

Alfa AF: 0.274 Hom.: 1894

Bravo AF: 0.203

Asia WGS AF: 0.106 AC: 371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.88
DANN	Benign	0.55

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: rs10843164; hg19: chr12-28569714;