12-28381482-G-C

Variant names:

• chr12-28381482-G-C
• rs2638953
• NM_018318.5:c.655-9822G>C

Variant summary

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

The NM_018318.5(CCDC91):​c.655-9822G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 151,922 control chromosomes in the GnomAD database, including 36,178 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 0.68 (36178 hom., cov: 31)
• Consequence: CCDC91 NM_018318.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.927
• Publications: 44 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC91	NM_018318.5	c.655-9822G>C		intron_variant	Intron 7 of 12	ENST00000536442.6	NP_060788.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC91	ENST00000536442.6	c.655-9822G>C		intron_variant	Intron 7 of 12	5	NM_018318.5	ENSP00000445660.2

Frequencies

GnomAD3 genomes AF: 0.685 AC: 103922 AN: 151804 Hom.: 36144 Cov.: 31

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.955

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.696

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

GnomAD4 genome AF: 0.685 AC: 104010 AN: 151922 Hom.: 36178 Cov.: 31 AF XY: 0.692 AC XY: 51384 AN XY: 74248

African (AFR) AF: 0.598 AC: 24762 AN: 41426

American (AMR) AF: 0.777 AC: 11844 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.705 AC: 2445 AN: 3470

East Asian (EAS) AF: 0.954 AC: 4938 AN: 5174

South Asian (SAS) AF: 0.819 AC: 3951 AN: 4826

European-Finnish (FIN) AF: 0.701 AC: 7394 AN: 10542

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.683 AC: 46388 AN: 67942

Other (OTH) AF: 0.699 AC: 1462 AN: 2092

Alfa AF: 0.686 Hom.: 17716

Bravo AF: 0.685

Asia WGS AF: 0.873 AC: 3028 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.16
DANN	Benign	0.44
PhyloP100		-0.93
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: rs2638953; hg19: chr12-28534415;