12-95894807-A-G

Position:

• chr12-95894807-A-G

Variant summary

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

The NM_182496.3(CCDC38):​c.772+182T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,146 control chromosomes in the GnomAD database, including 2,842 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 0.19 (2842 hom., cov: 32)
• Consequence: CCDC38 NM_182496.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.757

Genes affected

CCDC38 (HGNC:26843): (coiled-coil domain containing 38) Located in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

SNRPF (HGNC:11162): (small nuclear ribonucleoprotein polypeptide F) Enables RNA binding activity. Involved in spliceosomal snRNP assembly. Located in cytosol and nucleus. Part of several cellular components, including methylosome; nucleus; and pICln-Sm protein complex. Biomarker of nasopharynx carcinoma. [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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC38	NM_182496.3	c.772+182T>C		intron_variant		ENST00000344280.8	NP_872302.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC38	ENST00000344280.8	c.772+182T>C		intron_variant		1	NM_182496.3	ENSP00000345470.3
SNRPF	ENST00000552085.1	c.286+5626A>G		intron_variant		3		ENSP00000447127.1

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28663 AN: 152028 Hom.: 2843 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.0639

Gnomad SAS AF: 0.0887

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.188 AC: 28676 AN: 152146 Hom.: 2842 Cov.: 32 AF XY: 0.188 AC XY: 13963 AN XY: 74390

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.0640

Gnomad4 SAS AF: 0.0890

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.188

Alfa AF: 0.173 Hom.: 836

Bravo AF: 0.186

Asia WGS AF: 0.0680 AC: 240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.64

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: rs11108320; hg19: chr12-96288585;