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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395208.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMCO2	NM_001395208.2	MANE Select	c.-10-1995T>C		intron	N/A	NP_001382137.1	A6NFE2
	SMCO2	NM_001145010.3		c.-11+1652T>C		intron	N/A	NP_001138482.1	A6NFE2
	SMCO2	NM_001387218.3		c.-3-6159T>C		intron	N/A	NP_001374147.1	A0A8V8TM60

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMCO2	ENST00000535986.2	TSL:5 MANE Select	c.-10-1995T>C		intron	N/A	ENSP00000441688.1	A6NFE2
	SMCO2	ENST00000298876.8	TSL:5	c.-11+1652T>C		intron	N/A	ENSP00000298876.4	J3KNC3
	SMCO2	ENST00000698358.1		c.-3-6159T>C		intron	N/A	ENSP00000513681.1	A0A8V8TM60

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 v4.9

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;