rs6743259

Variant names:

• chr2-17733972-G-C
• rs6743259
• NM_001142286.2:c.345-2095C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142286.2(SMC6):​c.345-2095C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0853 in 152,196 control chromosomes in the GnomAD database, including 907 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 0.085 (907 hom., cov: 32)
• Consequence: SMC6 NM_001142286.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139
• Publications: 3 publications found

Genes affected

SMC6 (HGNC:20466): (structural maintenance of chromosomes 6) Enables ubiquitin protein ligase binding activity. Involved in several processes, including cellular senescence; positive regulation of chromosome segregation; and telomere maintenance via recombination. Located in chromosome and nuclear body. Part of Smc5-Smc6 complex. [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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142286.2. 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
	SMC6	NM_001142286.2	MANE Select	c.345-2095C>G		intron	N/A	NP_001135758.1	Q96SB8-1
	SMC6	NM_024624.6		c.345-2095C>G		intron	N/A	NP_078900.1	A0A2S1ZR87

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMC6	ENST00000448223.7	TSL:1 MANE Select	c.345-2095C>G		intron	N/A	ENSP00000404092.2	Q96SB8-1
	SMC6	ENST00000351948.8	TSL:1	c.345-2095C>G		intron	N/A	ENSP00000323439.4	Q96SB8-1
	SMC6	ENST00000446852.5	TSL:1	c.423-2095C>G		intron	N/A	ENSP00000408644.1	C9JMN1

Frequencies

GnomAD3 genomes AF: 0.0853 AC: 12967 AN: 152078 Hom.: 907 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.0570

Gnomad ASJ AF: 0.0435

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0288

Gnomad FIN AF: 0.0249

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0495

Gnomad OTH AF: 0.0789

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

GnomAD4 genome AF: 0.0853 AC: 12986 AN: 152196 Hom.: 907 Cov.: 32 AF XY: 0.0821 AC XY: 6114 AN XY: 74430

African (AFR) AF: 0.192 AC: 7965 AN: 41528

American (AMR) AF: 0.0568 AC: 869 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0435 AC: 151 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.0290 AC: 140 AN: 4828

European-Finnish (FIN) AF: 0.0249 AC: 264 AN: 10606

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0495 AC: 3362 AN: 67966

Other (OTH) AF: 0.0781 AC: 165 AN: 2114

Alfa AF: 0.0716 Hom.: 81

Bravo AF: 0.0933

Asia WGS AF: 0.0250 AC: 85 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.68
PhyloP100		0.14
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: rs6743259; hg19: chr2-17915239;