rs11656931

chr17-1814401-A-Gchr17-1814401-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052928.3(SMYD4):c.135-2286T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 152,222 control chromosomes in the GnomAD database, including 35,026 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 0.66 (35026 hom., cov: 34)
• Consequence: SMYD4 NM_052928.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30

Genes affected

SMYD4 (HGNC:21067): (SET and MYND domain containing 4) Predicted to enable metal ion binding activity and methyltransferase activity. Involved in heart development. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMYD4	NM_052928.3	c.135-2286T>C		intron_variant		ENST00000305513.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMYD4	ENST00000305513.12	c.135-2286T>C		intron_variant		1	NM_052928.3	P1

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100990 AN: 152104 Hom.: 35025 Cov.: 34

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.884

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.664

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

GnomAD4 genome AF: 0.664 AC: 101018 AN: 152222 Hom.: 35026 Cov.: 34 AF XY: 0.652 AC XY: 48563 AN XY: 74428

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.698

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.519

Gnomad4 FIN AF: 0.666

Gnomad4 NFE AF: 0.796

Gnomad4 OTH AF: 0.664

Alfa AF: 0.744 Hom.: 37233

Bravo AF: 0.647

Asia WGS AF: 0.452 AC: 1576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	8.5
Dann	Benign	0.53

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: rs11656931; hg19: chr17-1717695; COSMIC: COSV59713333;