rs6743259

Positions:

• chr2-17733972-G-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMC6	NM_001142286.2	c.345-2095C>G		intron_variant		ENST00000448223.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMC6	ENST00000448223.7	c.345-2095C>G		intron_variant		1	NM_001142286.2	P1

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

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.0568

Gnomad4 ASJ AF: 0.0435

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0290

Gnomad4 FIN AF: 0.0249

Gnomad4 NFE AF: 0.0495

Gnomad4 OTH AF: 0.0781

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.68

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: rs6743259; hg19: chr2-17915239;