rs2919856

Positions:

• chr2-88089019-A-T

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SMYD1	NM_198274.4	c.528+944A>T		intron_variant		ENST00000419482.7	NP_938015.1
SMYD1	NM_001330364.2	c.528+944A>T		intron_variant			NP_001317293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMYD1	ENST00000419482.7	c.528+944A>T		intron_variant		1	NM_198274.4	ENSP00000393453.2
SMYD1	ENST00000444564.2	c.528+944A>T		intron_variant		5		ENSP00000407888.2
SMYD1	ENST00000438570.1	c.294+4547A>T		intron_variant		2		ENSP00000387482.1
SMYD1	ENST00000468008.1	n.558+944A>T		intron_variant		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

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.455

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.525

Gnomad4 NFE AF: 0.554

Gnomad4 OTH AF: 0.469

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

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: rs2919856; hg19: chr2-88388538;