rs1834619

Positions:

• chr2-17720218-G-A
• chr2-17720218-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000448223.7(SMC6):​c.945+722C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,168 control chromosomes in the GnomAD database, including 2,821 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 0.11 (2821 hom., cov: 32)
• Consequence: SMC6 ENST00000448223.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMC6	NM_001142286.2	c.945+722C>T		intron_variant		ENST00000448223.7	NP_001135758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMC6	ENST00000448223.7	c.945+722C>T		intron_variant		1	NM_001142286.2	ENSP00000404092	P1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16395 AN: 152050 Hom.: 2802 Cov.: 32

Gnomad AFR AF: 0.0193

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.0263

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0537

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.108 AC: 16430 AN: 152168 Hom.: 2821 Cov.: 32 AF XY: 0.123 AC XY: 9115 AN XY: 74380

Gnomad4 AFR AF: 0.0192

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.0263

Gnomad4 EAS AF: 0.697

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.0537

Gnomad4 OTH AF: 0.133

Alfa AF: 0.0664 Hom.: 1011

Bravo AF: 0.121

Asia WGS AF: 0.503 AC: 1746 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.32
DANN	Benign	0.27

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: rs1834619; hg19: chr2-17901485;