rs7503422

chr17-1812141-G-A

Variant summary

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

The NM_052928.3(SMYD4):c.135-26C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.753 in 1,604,564 control chromosomes in the GnomAD database, including 464,955 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 0.73 (41285 hom., cov: 32)
  • Exomes 𝑓: 0.76 (423670 hom.)
• Consequence: SMYD4 NM_052928.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMYD4	NM_052928.3	c.135-26C>T		intron_variant		ENST00000305513.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMYD4	ENST00000305513.12	c.135-26C>T		intron_variant		1	NM_052928.3	P1

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110726 AN: 151992 Hom.: 41255 Cov.: 32

Gnomad AFR AF: 0.752

Gnomad AMI AF: 0.884

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.713

GnomAD3 exomes AF: 0.666 AC: 161860 AN: 243138 Hom.: 57062 AF XY: 0.670 AC XY: 88356 AN XY: 131814

Gnomad AFR exome AF: 0.754

Gnomad AMR exome AF: 0.406

Gnomad ASJ exome AF: 0.685

Gnomad EAS exome AF: 0.468

Gnomad SAS exome AF: 0.535

Gnomad FIN exome AF: 0.667

Gnomad NFE exome AF: 0.791

Gnomad OTH exome AF: 0.696

GnomAD4 exome AF: 0.756 AC: 1098071 AN: 1452454 Hom.: 423670 Cov.: 38 AF XY: 0.750 AC XY: 542196 AN XY: 722564

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 0.421

Gnomad4 ASJ exome AF: 0.692

Gnomad4 EAS exome AF: 0.487

Gnomad4 SAS exome AF: 0.536

Gnomad4 FIN exome AF: 0.681

Gnomad4 NFE exome AF: 0.802

Gnomad4 OTH exome AF: 0.736

GnomAD4 genome AF: 0.728 AC: 110809 AN: 152110 Hom.: 41285 Cov.: 32 AF XY: 0.716 AC XY: 53213 AN XY: 74350

Gnomad4 AFR AF: 0.752

Gnomad4 AMR AF: 0.556

Gnomad4 ASJ AF: 0.699

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.666

Gnomad4 NFE AF: 0.797

Gnomad4 OTH AF: 0.713

Alfa AF: 0.761 Hom.: 61610

Bravo AF: 0.720

Asia WGS AF: 0.468 AC: 1633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.5
Dann	Benign	0.57

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: rs7503422; hg19: chr17-1715435; COSMIC: COSV59711583;