chr12-28416781-T-C

Variant names:

• chr12-28416781-T-C
• rs10843164
• NM_018318.5:c.762+25370T>C

Variant summary

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

The ENST00000536442.6(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 ENST00000536442.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 21 publications found

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]

CCDC91 Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• punctate palmoplantar keratoderma

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000536442.6. 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
	CCDC91	NM_018318.5	MANE Select	c.762+25370T>C		intron	N/A	NP_060788.3
	CCDC91	NM_001352078.2		c.762+25370T>C		intron	N/A	NP_001339007.1
	CCDC91	NM_001352079.2		c.762+25370T>C		intron	N/A	NP_001339008.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC91	ENST00000536442.6	TSL:5 MANE Select	c.762+25370T>C		intron	N/A	ENSP00000445660.2
	CCDC91	ENST00000381259.5	TSL:1	c.762+25370T>C		intron	N/A	ENSP00000370658.1
	CCDC91	ENST00000540401.5	TSL:1	n.854+25370T>C		intron	N/A

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

African (AFR) AF: 0.0977 AC: 4054 AN: 41484

American (AMR) AF: 0.166 AC: 2537 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 799 AN: 3470

East Asian (EAS) AF: 0.0470 AC: 243 AN: 5172

South Asian (SAS) AF: 0.177 AC: 852 AN: 4812

European-Finnish (FIN) AF: 0.292 AC: 3076 AN: 10548

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.305 AC: 20716 AN: 67946

Other (OTH) AF: 0.218 AC: 459 AN: 2108

Alfa AF: 0.268 Hom.: 11976

Bravo AF: 0.203

Asia WGS AF: 0.106 AC: 371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.88
DANN	Benign	0.55
PhyloP100		-1.4
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: rs10843164; hg19: chr12-28569714;