rs10843150

Positions:

• chr12-28304869-A-G
• chr12-28304869-A-T

Variant summary

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

The NM_018318.5(CCDC91):​c.110-780A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,060 control chromosomes in the GnomAD database, including 4,018 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 0.20 (4018 hom., cov: 32)
• Consequence: CCDC91 NM_018318.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.508

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC91	NM_018318.5	c.110-780A>G		intron_variant		ENST00000536442.6	NP_060788.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC91	ENST00000536442.6	c.110-780A>G		intron_variant		5	NM_018318.5	ENSP00000445660	P1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30759 AN: 151942 Hom.: 4019 Cov.: 32

Gnomad AFR AF: 0.0586

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.0456

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.202 AC: 30770 AN: 152060 Hom.: 4018 Cov.: 32 AF XY: 0.198 AC XY: 14749 AN XY: 74312

Gnomad4 AFR AF: 0.0587

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.0459

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.207

Alfa AF: 0.248 Hom.: 1387

Bravo AF: 0.187

Asia WGS AF: 0.100 AC: 352 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.4
DANN	Benign	0.29

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: rs10843150; hg19: chr12-28457802;