17-1814401-A-G

Variant names:

• chr17-1814401-A-G
• rs11656931
• NM_052928.3:c.135-2286T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SMYD4	NM_052928.3	c.135-2286T>C		intron_variant	Intron 2 of 10	ENST00000305513.12	NP_443160.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMYD4	ENST00000305513.12	c.135-2286T>C		intron_variant	Intron 2 of 10	1	NM_052928.3	ENSP00000304360.7

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

African (AFR) AF: 0.529 AC: 21975 AN: 41522

American (AMR) AF: 0.527 AC: 8061 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.698 AC: 2425 AN: 3472

East Asian (EAS) AF: 0.472 AC: 2445 AN: 5184

South Asian (SAS) AF: 0.519 AC: 2510 AN: 4832

European-Finnish (FIN) AF: 0.666 AC: 7048 AN: 10590

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.796 AC: 54138 AN: 68014

Other (OTH) AF: 0.664 AC: 1403 AN: 2112

Alfa AF: 0.745 Hom.: 44682

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
PhyloP100		1.3
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: rs11656931; hg19: chr17-1717695; COSMIC: COSV59713333;