rs300291

Variant names:

• chr18-2771518-G-T
• rs300291
• NM_015295.3:c.4967-15G>T

Your query was ambiguous. Multiple possible variants found:

• chr18-2771518-G-T
• chr18-2771518-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015295.3(SMCHD1):​c.4967-15G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.997 in 1,546,432 control chromosomes in the GnomAD database, including 768,695 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.98 (73791 hom., cov: 32)
  • Exomes 𝑓: 1.0 (694904 hom.)
• Consequence: SMCHD1 NM_015295.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.982
• Publications: 7 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: PanelApp Australia, Ambry Genetics, Illumina, ClinGen, G2P, Labcorp Genetics (formerly Invitae)
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 18-2771518-G-T is Benign according to our data. Variant chr18-2771518-G-T is described in ClinVar as Benign. ClinVar VariationId is 260652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 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.4967-15G>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.4967-15G>T		intron	N/A	ENSP00000326603.7	A6NHR9-1
	SMCHD1	ENST00000939310.1		c.4880-15G>T		intron	N/A	ENSP00000609369.1
	SMCHD1	ENST00000688342.1		c.4835-15G>T		intron	N/A	ENSP00000508422.1	A0A8I5KRS9

Frequencies

GnomAD3 genomes AF: 0.984 AC: 149774 AN: 152206 Hom.: 73738 Cov.: 32

Gnomad AFR AF: 0.944

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.994

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.989

GnomAD2 exomes AF: 0.996 AC: 190726 AN: 191538 AF XY: 0.997

Gnomad AFR exome AF: 0.940

Gnomad AMR exome AF: 0.997

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.998

GnomAD4 exome AF: 0.998 AC: 1391898 AN: 1394108 Hom.: 694904 Cov.: 26 AF XY: 0.999 AC XY: 692874 AN XY: 693846

African (AFR) AF: 0.941 AC: 26933 AN: 28628

American (AMR) AF: 0.997 AC: 25597 AN: 25686

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 23984 AN: 23984

East Asian (EAS) AF: 1.00 AC: 36026 AN: 36026

South Asian (SAS) AF: 1.00 AC: 74309 AN: 74318

European-Finnish (FIN) AF: 1.00 AC: 52818 AN: 52818

Middle Eastern (MID) AF: 0.995 AC: 5576 AN: 5606

European-Non Finnish (NFE) AF: 1.00 AC: 1089387 AN: 1089512

Other (OTH) AF: 0.995 AC: 57268 AN: 57530

GnomAD4 genome AF: 0.984 AC: 149886 AN: 152324 Hom.: 73791 Cov.: 32 AF XY: 0.984 AC XY: 73276 AN XY: 74484

African (AFR) AF: 0.945 AC: 39261 AN: 41568

American (AMR) AF: 0.994 AC: 15211 AN: 15304

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5190 AN: 5190

South Asian (SAS) AF: 1.00 AC: 4828 AN: 4830

European-Finnish (FIN) AF: 1.00 AC: 10614 AN: 10614

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68014 AN: 68026

Other (OTH) AF: 0.989 AC: 2091 AN: 2114

Alfa AF: 0.977 Hom.: 22252

Bravo AF: 0.981

Asia WGS AF: 0.998 AC: 3452 AN: 3460

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Arrhinia with choanal atresia and microphthalmia syndrome (1)
-	-	1	Facioscapulohumeral muscular dystrophy 2 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.6
DANN	Benign	0.43
PhyloP100		0.98
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs300291;

hg19: chr18-2771516;