rs6716388

Variant names:

• chr2-17704471-C-G
• rs6716388
• NM_001142286.2:c.2007-1179G>C

Variant summary

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

The NM_001142286.2(SMC6):​c.2007-1179G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 152,008 control chromosomes in the GnomAD database, including 22,650 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 0.51 (22650 hom., cov: 32)
• Consequence: SMC6 NM_001142286.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMC6	NM_001142286.2	c.2007-1179G>C		intron_variant	Intron 18 of 27	ENST00000448223.7	NP_001135758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMC6	ENST00000448223.7	c.2007-1179G>C		intron_variant	Intron 18 of 27	1	NM_001142286.2	ENSP00000404092.2
SMC6	ENST00000351948.8	c.2007-1179G>C		intron_variant	Intron 17 of 26	1		ENSP00000323439.4
SMC6	ENST00000446852.5	c.2085-1179G>C		intron_variant	Intron 19 of 19	1		ENSP00000408644.1
SMC6	ENST00000402989.5	c.2007-1179G>C		intron_variant	Intron 20 of 29	2		ENSP00000384539.1

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77808 AN: 151890 Hom.: 22618 Cov.: 32

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.0818

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.512 AC: 77889 AN: 152008 Hom.: 22650 Cov.: 32 AF XY: 0.504 AC XY: 37478 AN XY: 74300

African (AFR) AF: 0.781 AC: 32384 AN: 41482

American (AMR) AF: 0.368 AC: 5616 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1587 AN: 3472

East Asian (EAS) AF: 0.0819 AC: 424 AN: 5174

South Asian (SAS) AF: 0.205 AC: 989 AN: 4816

European-Finnish (FIN) AF: 0.476 AC: 5015 AN: 10530

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.447 AC: 30407 AN: 67952

Other (OTH) AF: 0.484 AC: 1023 AN: 2114

Alfa AF: 0.503 Hom.: 2542

Bravo AF: 0.518

Asia WGS AF: 0.183 AC: 639 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.79
PhyloP100		-0.28
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: rs6716388; hg19: chr2-17885738;