18-2733992-C-T

Variant names:

• chr18-2733992-C-T
• rs1893123
• NM_015295.3:c.3276+1500C>T

Variant summary

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

The NM_015295.3(SMCHD1):​c.3276+1500C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 152,014 control chromosomes in the GnomAD database, including 26,196 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 0.58 (26196 hom., cov: 31)
• Consequence: SMCHD1 NM_015295.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.507
• Publications: 5 publications found

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]

SMCHD1 Gene-Disease associations (from GenCC):

• arhinia, choanal atresia, and microphthalmia

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Illumina, PanelApp Australia, G2P
• facioscapulohumeral muscular dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hyposmia-nasal and ocular hypoplasia-hypogonadotropic hypogonadism syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000266049 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015295.3. 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
	SMCHD1	NM_015295.3	MANE Select	c.3276+1500C>T		intron	N/A	NP_056110.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMCHD1	ENST00000320876.11	TSL:5 MANE Select	c.3276+1500C>T		intron	N/A	ENSP00000326603.7	A6NHR9-1
	SMCHD1	ENST00000939310.1		c.3189+1500C>T		intron	N/A	ENSP00000609369.1
	SMCHD1	ENST00000688342.1		c.3276+1500C>T		intron	N/A	ENSP00000508422.1	A0A8I5KRS9

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88426 AN: 151896 Hom.: 26166 Cov.: 31

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.582 AC: 88512 AN: 152014 Hom.: 26196 Cov.: 31 AF XY: 0.584 AC XY: 43414 AN XY: 74314

African (AFR) AF: 0.612 AC: 25382 AN: 41456

American (AMR) AF: 0.587 AC: 8975 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 2322 AN: 3470

East Asian (EAS) AF: 0.812 AC: 4199 AN: 5174

South Asian (SAS) AF: 0.790 AC: 3810 AN: 4824

European-Finnish (FIN) AF: 0.506 AC: 5346 AN: 10556

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.536 AC: 36393 AN: 67936

Other (OTH) AF: 0.605 AC: 1278 AN: 2114

Alfa AF: 0.558 Hom.: 62263

Bravo AF: 0.593

Asia WGS AF: 0.809 AC: 2812 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.53
PhyloP100		0.51
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: rs1893123; hg19: chr18-2733990;