rs559994

Positions:

• chr18-2804131-G-A
• chr18-2804131-G-C

Variant summary

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

The NM_015295.3(SMCHD1):​c.*1579G>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 0.316 in 152,008 control chromosomes in the GnomAD database, including 9,114 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 0.32 (9114 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SMCHD1 NM_015295.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91

Genes affected

SMCHD1 (HGNC:29090): (structural maintenance of chromosomes flexible hinge domain containing 1) This gene encodes a protein which contains a hinge region domain found in members of the SMC (structural maintenance of chromosomes) protein family. [provided by RefSeq, Dec 2011]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMCHD1	NM_015295.3	c.*1579G>A		3_prime_UTR_variant	48/48	ENST00000320876.11	NP_056110.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMCHD1	ENST00000320876.11	c.*1579G>A		3_prime_UTR_variant	48/48	5	NM_015295.3	ENSP00000326603	P2
	ENST00000583546.1	n.370+4324C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.316 AC: 48073 AN: 151890 Hom.: 9118 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.318

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.316 AC: 48066 AN: 152008 Hom.: 9114 Cov.: 32 AF XY: 0.316 AC XY: 23499 AN XY: 74284

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.436

Gnomad4 NFE AF: 0.430

Gnomad4 OTH AF: 0.317

Alfa AF: 0.401 Hom.: 12391

Bravo AF: 0.299

Asia WGS AF: 0.164 AC: 572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.4
DANN	Benign	0.44

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: rs559994; hg19: chr18-2804129;