Genetic Variant SMYD4:c.2261+481G>A (chr17-1782554-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_052928.3(SMYD4):c.2261+481G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 150,144 control chromosomes in the GnomAD database, including 10,647 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 0.37 ( 10627 hom., cov: 27)

Exomes 𝑓: 0.29 ( 20 hom. )

Consequence

SMYD4
NM_052928.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.516

Publications

12 publications found

Variant links:

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]

SMYD4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SMYD4	NM_052928.3 link	c.2261+481G>A	intron_variant	Intron 10 of 10	ENST00000305513.12	NP_443160.2	Q8IYR2
SMYD4	XM_024450560.2 link	c.2261+481G>A	intron_variant	Intron 10 of 10		XP_024306328.1
SMYD4	XM_047435291.1 link	c.1949+481G>A	intron_variant	Intron 9 of 9		XP_047291247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMYD4	ENST00000305513.12 link	c.2261+481G>A		intron_variant	Intron 10 of 10	1	NM_052928.3	ENSP00000304360.7		Q8IYR2
SMYD4	ENST00000491788.1 link	c.*477G>A		3_prime_UTR_variant	Exon 6 of 6	2		ENSP00000460921.1		I3L428

Frequencies

GnomAD3 genomes

AF:

0.372

AC:

55679

AN:

149716

Hom.:

10613

Cov.:

show subpopulations

Gnomad AFR

AF:

0.372

Gnomad AMI

AF:

0.240

Gnomad AMR

AF:

0.463

Gnomad ASJ

AF:

0.381

Gnomad EAS

AF:

0.504

Gnomad SAS

AF:

0.429

Gnomad FIN

AF:

0.425

Gnomad MID

AF:

0.268

Gnomad NFE

AF:

0.332

Gnomad OTH

AF:

0.355

GnomAD4 exome

AF:

0.288

AC:

102

AN:

354

Hom.:

Cov.:

AF XY:

0.314

AC XY:

AN XY:

204

show subpopulations

African (AFR)

AF:

0.333

AC:

AN:

American (AMR)

AF:

0.600

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.667

AC:

AN:

South Asian (SAS)

AF:

0.455

AC:

AN:

European-Finnish (FIN)

AF:

0.550

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.248

AC:

AN:

270

Other (OTH)

AF:

0.125

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.372

AC:

55727

AN:

149790

Hom.:

10627

Cov.:

AF XY:

0.378

AC XY:

27504

AN XY:

72838

show subpopulations

African (AFR)

AF:

0.372

AC:

15107

AN:

40590

American (AMR)

AF:

0.464

AC:

6935

AN:

14952

Ashkenazi Jewish (ASJ)

AF:

0.381

AC:

1319

AN:

3464

East Asian (EAS)

AF:

0.505

AC:

2570

AN:

5092

South Asian (SAS)

AF:

0.429

AC:

2041

AN:

4754

European-Finnish (FIN)

AF:

0.425

AC:

4214

AN:

9920

Middle Eastern (MID)

AF:

0.276

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.332

AC:

22506

AN:

67750

Other (OTH)

AF:

0.356

AC:

737

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1709

3418

5126

6835

8544

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

534

1068

1602

2136

2670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.364

Hom.:

2268

Bravo

AF:

0.376

Asia WGS

AF:

0.476

AC:

1652

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

8.9

(source)

DANN

Benign

0.58

PhyloP100

0.52

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over