rs306640

Variant names:

• chr12-27468627-T-C
• rs306640
• NM_001395208.2:c.-10-1995T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SMCO2	NM_001395208.2	c.-10-1995T>C		intron_variant	Intron 1 of 8	ENST00000535986.2	NP_001382137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMCO2	ENST00000535986.2	c.-10-1995T>C		intron_variant	Intron 1 of 8	5	NM_001395208.2	ENSP00000441688.1
SMCO2	ENST00000298876.8	c.-11+1652T>C		intron_variant	Intron 1 of 7	5		ENSP00000298876.4
SMCO2	ENST00000698358.1	c.-3-6159T>C		intron_variant	Intron 1 of 5			ENSP00000513681.1

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

African (AFR) AF: 0.220 AC: 9105 AN: 41480

American (AMR) AF: 0.0623 AC: 953 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0939 AC: 326 AN: 3470

East Asian (EAS) AF: 0.116 AC: 601 AN: 5182

South Asian (SAS) AF: 0.0909 AC: 438 AN: 4818

European-Finnish (FIN) AF: 0.0313 AC: 332 AN: 10620

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0501 AC: 3410 AN: 68030

Other (OTH) AF: 0.0818 AC: 173 AN: 2116

Alfa AF: 0.0827 Hom.: 115

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
PhyloP100		-0.60
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: rs306640; hg19: chr12-27621560;