rs10506039

chr12-28534398-A-G

Variant summary

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

The NM_018318.5(CCDC91):c.1216-14665A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0803 in 152,168 control chromosomes in the GnomAD database, including 1,485 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 0.080 (1485 hom., cov: 32)
• Consequence: CCDC91 NM_018318.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC91	NM_018318.5	c.1216-14665A>G		intron_variant		ENST00000536442.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC91	ENST00000536442.6	c.1216-14665A>G		intron_variant		5	NM_018318.5	P1

Frequencies

GnomAD3 genomes AF: 0.0802 AC: 12200 AN: 152050 Hom.: 1485 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0384

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00435

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.00316

Gnomad OTH AF: 0.0651

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

GnomAD4 genome AF: 0.0803 AC: 12223 AN: 152168 Hom.: 1485 Cov.: 32 AF XY: 0.0787 AC XY: 5858 AN XY: 74402

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.0383

Gnomad4 ASJ AF: 0.0536

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00414

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00318

Gnomad4 OTH AF: 0.0644

Alfa AF: 0.0489 Hom.: 93

Bravo AF: 0.0927

Asia WGS AF: 0.0200 AC: 70 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.49
Dann	Benign	0.87

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: rs10506039; hg19: chr12-28687331;