12-28362948-A-T

Position:

• chr12-28362948-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.654+433A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0315 in 152,148 control chromosomes in the GnomAD database, including 123 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 0.032 (123 hom., cov: 33)
• Consequence: CCDC91 NM_018318.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.409

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC91	NM_018318.5	c.654+433A>T		intron_variant		ENST00000536442.6	NP_060788.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC91	ENST00000536442.6	c.654+433A>T		intron_variant		5	NM_018318.5	ENSP00000445660.2

Frequencies

GnomAD3 genomes AF: 0.0316 AC: 4801 AN: 152030 Hom.: 123 Cov.: 33

Gnomad AFR AF: 0.00723

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.0250

Gnomad ASJ AF: 0.0935

Gnomad EAS AF: 0.0142

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0431

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0367

Gnomad OTH AF: 0.0325

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

GnomAD4 genome AF: 0.0315 AC: 4799 AN: 152148 Hom.: 123 Cov.: 33 AF XY: 0.0331 AC XY: 2459 AN XY: 74396

Gnomad4 AFR AF: 0.00721

Gnomad4 AMR AF: 0.0249

Gnomad4 ASJ AF: 0.0935

Gnomad4 EAS AF: 0.0143

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.0431

Gnomad4 NFE AF: 0.0367

Gnomad4 OTH AF: 0.0322

Alfa AF: 0.0322 Hom.: 13

Bravo AF: 0.0273

Asia WGS AF: 0.0550 AC: 186 AN: 3426

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.35

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: rs10506030; hg19: chr12-28515881;