rs2919856

Variant names:

• chr2-88089019-A-T
• rs2919856
• NM_198274.4:c.528+944A>T

Variant summary

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

The NM_198274.4(SMYD1):​c.528+944A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 152,040 control chromosomes in the GnomAD database, including 17,603 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 0.47 (17603 hom., cov: 32)
• Consequence: SMYD1 NM_198274.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180
• Publications: 3 publications found

Genes affected

SMYD1 (HGNC:20986): (SET and MYND domain containing 1) Predicted to enable histone-lysine N-methyltransferase activity. Involved in positive regulation of myoblast differentiation and positive regulation of myotube differentiation. Predicted to be located in cytoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SMYD1 Gene-Disease associations (from GenCC):

• hypertrophic cardiomyopathy

  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 = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMYD1	NM_198274.4	c.528+944A>T		intron_variant	Intron 3 of 9	ENST00000419482.7	NP_938015.1
SMYD1	NM_001330364.2	c.528+944A>T		intron_variant	Intron 3 of 8		NP_001317293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMYD1	ENST00000419482.7	c.528+944A>T		intron_variant	Intron 3 of 9	1	NM_198274.4	ENSP00000393453.2
SMYD1	ENST00000444564.2	c.528+944A>T		intron_variant	Intron 3 of 8	5		ENSP00000407888.2
SMYD1	ENST00000438570.1	c.294+4547A>T		intron_variant	Intron 2 of 2	2		ENSP00000387482.1
SMYD1	ENST00000468008.1	n.558+944A>T		intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71554 AN: 151922 Hom.: 17604 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.471 AC: 71571 AN: 152040 Hom.: 17603 Cov.: 32 AF XY: 0.468 AC XY: 34769 AN XY: 74316

African (AFR) AF: 0.364 AC: 15110 AN: 41466

American (AMR) AF: 0.455 AC: 6960 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1658 AN: 3470

East Asian (EAS) AF: 0.190 AC: 982 AN: 5176

South Asian (SAS) AF: 0.417 AC: 2007 AN: 4810

European-Finnish (FIN) AF: 0.525 AC: 5546 AN: 10564

Middle Eastern (MID) AF: 0.568 AC: 166 AN: 292

European-Non Finnish (NFE) AF: 0.554 AC: 37635 AN: 67954

Other (OTH) AF: 0.469 AC: 988 AN: 2106

Alfa AF: 0.508 Hom.: 2515

Bravo AF: 0.461

Asia WGS AF: 0.291 AC: 1013 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.93
DANN	Benign	0.80
PhyloP100		0.18
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: rs2919856; hg19: chr2-88388538;