12-28458846-T-C

Variant names:

• chr12-28458846-T-C
• rs7313862
• NM_018318.5:c.1101+6192T>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.1101+6192T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 151,946 control chromosomes in the GnomAD database, including 9,398 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 0.34 (9398 hom., cov: 31)
• Consequence: CCDC91 NM_018318.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109
• Publications: 4 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018318.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC91	NM_018318.5	MANE Select	c.1101+6192T>C		intron	N/A	NP_060788.3
	CCDC91	NM_001352078.2		c.1101+6192T>C		intron	N/A	NP_001339007.1
	CCDC91	NM_001352079.2		c.1101+6192T>C		intron	N/A	NP_001339008.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC91	ENST00000536442.6	TSL:5 MANE Select	c.1101+6192T>C		intron	N/A	ENSP00000445660.2
	CCDC91	ENST00000381259.5	TSL:1	c.1101+6192T>C		intron	N/A	ENSP00000370658.1
	CCDC91	ENST00000540401.5	TSL:1	n.1193+6192T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51127 AN: 151828 Hom.: 9386 Cov.: 31

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.0468

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.337 AC: 51175 AN: 151946 Hom.: 9398 Cov.: 31 AF XY: 0.328 AC XY: 24347 AN XY: 74266

African (AFR) AF: 0.457 AC: 18904 AN: 41392

American (AMR) AF: 0.231 AC: 3525 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1098 AN: 3466

East Asian (EAS) AF: 0.0471 AC: 244 AN: 5180

South Asian (SAS) AF: 0.189 AC: 913 AN: 4822

European-Finnish (FIN) AF: 0.300 AC: 3164 AN: 10564

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22276 AN: 67968

Other (OTH) AF: 0.316 AC: 666 AN: 2108

Alfa AF: 0.335 Hom.: 1451

Bravo AF: 0.339

Asia WGS AF: 0.135 AC: 474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.1
DANN	Benign	0.61
PhyloP100		-0.11
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: rs7313862; hg19: chr12-28611779;