rs115632137

Variant names:

• chr18-2740800-A-T
• rs115632137
• NM_015295.3:c.3612A>T

Your query was ambiguous. Multiple possible variants found:

• chr18-2740800-A-T
• chr18-2740800-A-C
• chr18-2740800-A-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_015295.3(SMCHD1):​c.3612A>T​(p.Ser1204Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00586 in 1,605,366 control chromosomes in the GnomAD database, including 471 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (244 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (227 hom.)
• Consequence: SMCHD1 NM_015295.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0650
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 18-2740800-A-T is Benign according to our data. Variant chr18-2740800-A-T is described in ClinVar as Benign. ClinVar VariationId is 260644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.065 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 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.3612A>T	p.Ser1204Ser	synonymous	Exon 28 of 48	NP_056110.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMCHD1	ENST00000320876.11	TSL:5 MANE Select	c.3612A>T	p.Ser1204Ser	synonymous	Exon 28 of 48	ENSP00000326603.7	A6NHR9-1
	SMCHD1	ENST00000939310.1		c.3525A>T	p.Ser1175Ser	synonymous	Exon 28 of 48	ENSP00000609369.1
	SMCHD1	ENST00000688342.1		c.3612A>T	p.Ser1204Ser	synonymous	Exon 28 of 47	ENSP00000508422.1	A0A8I5KRS9

Frequencies

GnomAD3 genomes AF: 0.0311 AC: 4736 AN: 152154 Hom.: 243 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0119

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.0239

GnomAD2 exomes AF: 0.00776 AC: 1911 AN: 246208 AF XY: 0.00599

Gnomad AFR exome AF: 0.109

Gnomad AMR exome AF: 0.00442

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000463

Gnomad OTH exome AF: 0.00489

GnomAD4 exome AF: 0.00321 AC: 4662 AN: 1453094 Hom.: 227 Cov.: 29 AF XY: 0.00277 AC XY: 2002 AN XY: 723040

African (AFR) AF: 0.112 AC: 3716 AN: 33196

American (AMR) AF: 0.00518 AC: 229 AN: 44206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25958

East Asian (EAS) AF: 0.00 AC: 0 AN: 39404

South Asian (SAS) AF: 0.000306 AC: 26 AN: 85004

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53234

Middle Eastern (MID) AF: 0.00575 AC: 33 AN: 5742

European-Non Finnish (NFE) AF: 0.000219 AC: 242 AN: 1106340

Other (OTH) AF: 0.00693 AC: 416 AN: 60010

GnomAD4 genome AF: 0.0311 AC: 4743 AN: 152272 Hom.: 244 Cov.: 32 AF XY: 0.0304 AC XY: 2267 AN XY: 74456

African (AFR) AF: 0.108 AC: 4467 AN: 41540

American (AMR) AF: 0.0118 AC: 181 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000603 AC: 41 AN: 68014

Other (OTH) AF: 0.0237 AC: 50 AN: 2112

Alfa AF: 0.00188 Hom.: 4

Bravo AF: 0.0353

Asia WGS AF: 0.00405 AC: 14 AN: 3470

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Facioscapulohumeral muscular dystrophy 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	8.3
DANN	Benign	0.85
PhyloP100		-0.065
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs115632137; hg19: chr18-2740798;