chr12-27468627-T-C

Position:

• chr12-27468627-T-C

Variant summary

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

The NM_001395208.2(SMCO2):​c.-10-1995T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,230 control chromosomes in the GnomAD database, including 1,246 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 0.10 (1246 hom., cov: 32)
• Consequence: SMCO2 NM_001395208.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.600

Genes affected

SMCO2 (HGNC:34448): (single-pass membrane protein with coiled-coil domains 2) Predicted to be integral component of membrane. [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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMCO2	NM_001395208.2	c.-10-1995T>C		intron_variant		ENST00000535986.2	NP_001382137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMCO2	ENST00000535986.2	c.-10-1995T>C		intron_variant		5	NM_001395208.2	ENSP00000441688
SMCO2	ENST00000298876.8	c.-11+1652T>C		intron_variant		5		ENSP00000298876	P1
SMCO2	ENST00000698358.1	c.-3-6159T>C		intron_variant				ENSP00000513681

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15354 AN: 152110 Hom.: 1242 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0623

Gnomad ASJ AF: 0.0939

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.0900

Gnomad FIN AF: 0.0313

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0501

Gnomad OTH AF: 0.0812

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

GnomAD4 genome AF: 0.101 AC: 15387 AN: 152230 Hom.: 1246 Cov.: 32 AF XY: 0.100 AC XY: 7452 AN XY: 74450

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.0623

Gnomad4 ASJ AF: 0.0939

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.0909

Gnomad4 FIN AF: 0.0313

Gnomad4 NFE AF: 0.0501

Gnomad4 OTH AF: 0.0818

Alfa AF: 0.0765 Hom.: 99

Bravo AF: 0.108

Asia WGS AF: 0.113 AC: 394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.6
DANN	Benign	0.74

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: rs306640; hg19: chr12-27621560;