rs3747238

Variant names:

• chr22-45344215-C-T
• rs3747238
• NM_148674.5:c.*341G>A

Variant summary

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

The NM_148674.5(SMC1B):​c.*341G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 162,354 control chromosomes in the GnomAD database, including 15,883 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 0.40 (14635 hom., cov: 34)
  • Exomes 𝑓: 0.49 (1248 hom.)
• Consequence: SMC1B NM_148674.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.882
• Publications: 19 publications found

Genes affected

SMC1B (HGNC:11112): (structural maintenance of chromosomes 1B) SMC1L2 belongs to a family of proteins required for chromatid cohesion and DNA recombination during meiosis and mitosis (3:Revenkova et al., 2001 [PubMed 11564881]).[supplied by OMIM, Mar 2008]

SMC1B Gene-Disease associations (from GenCC):

• gonadal dysgenesis

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_148674.5. 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
	SMC1B	NM_148674.5	MANE Select	c.*341G>A		3_prime_UTR	Exon 25 of 25	NP_683515.4
	SMC1B	NM_001291501.2		c.*341G>A		3_prime_UTR	Exon 23 of 23	NP_001278430.1	Q8NDV3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMC1B	ENST00000357450.9	TSL:5 MANE Select	c.*341G>A		3_prime_UTR	Exon 25 of 25	ENSP00000350036.4	Q8NDV3-3
	SMC1B	ENST00000877413.1		c.*341G>A		3_prime_UTR	Exon 23 of 23	ENSP00000547472.1
	SMC1B	ENST00000923332.1		c.*341G>A		3_prime_UTR	Exon 21 of 21	ENSP00000593391.1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60235 AN: 152054 Hom.: 14635 Cov.: 34

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.414

GnomAD4 exome AF: 0.488 AC: 4971 AN: 10182 Hom.: 1248 Cov.: 0 AF XY: 0.496 AC XY: 2604 AN XY: 5248

African (AFR) AF: 0.118 AC: 50 AN: 422

American (AMR) AF: 0.448 AC: 145 AN: 324

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 224 AN: 468

East Asian (EAS) AF: 0.436 AC: 251 AN: 576

South Asian (SAS) AF: 0.261 AC: 37 AN: 142

European-Finnish (FIN) AF: 0.464 AC: 168 AN: 362

Middle Eastern (MID) AF: 0.537 AC: 29 AN: 54

European-Non Finnish (NFE) AF: 0.528 AC: 3739 AN: 7088

Other (OTH) AF: 0.440 AC: 328 AN: 746

GnomAD4 genome AF: 0.396 AC: 60242 AN: 152172 Hom.: 14635 Cov.: 34 AF XY: 0.390 AC XY: 29030 AN XY: 74372

African (AFR) AF: 0.111 AC: 4602 AN: 41534

American (AMR) AF: 0.443 AC: 6766 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1716 AN: 3468

East Asian (EAS) AF: 0.337 AC: 1748 AN: 5184

South Asian (SAS) AF: 0.328 AC: 1584 AN: 4826

European-Finnish (FIN) AF: 0.467 AC: 4944 AN: 10576

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.551 AC: 37440 AN: 67988

Other (OTH) AF: 0.408 AC: 861 AN: 2108

Alfa AF: 0.493 Hom.: 14818

Bravo AF: 0.385

Asia WGS AF: 0.264 AC: 916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.75
DANN	Benign	0.29
PhyloP100		-0.88
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: rs3747238; hg19: chr22-45740096;