12-28381482-G-C

Position:

• chr12-28381482-G-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• 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/exons	MANE	Protein	UniProt
CCDC91	NM_018318.5	c.655-9822G>C		intron_variant		ENST00000536442.6	NP_060788.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC91	ENST00000536442.6	c.655-9822G>C		intron_variant		5	NM_018318.5	ENSP00000445660	P1

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

Gnomad4 AFR AF: 0.598

Gnomad4 AMR AF: 0.777

Gnomad4 ASJ AF: 0.705

Gnomad4 EAS AF: 0.954

Gnomad4 SAS AF: 0.819

Gnomad4 FIN AF: 0.701

Gnomad4 NFE AF: 0.683

Gnomad4 OTH AF: 0.699

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

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: rs2638953; hg19: chr12-28534415;