dbSNP rs7503422: SMYD4:c.135-26C>T (chr17-1812141-G-A) – 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.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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.140

Publications

15 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:

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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=-0.91).

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052928.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMYD4	NM_052928.3	MANE Select	c.135-26C>T		intron	N/A	NP_443160.2	Q8IYR2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SMYD4	ENST00000305513.12	TSL:1 MANE Select	c.135-26C>T	intron	N/A	ENSP00000304360.7	Q8IYR2
SMYD4	ENST00000954772.1		c.135-26C>T	intron	N/A	ENSP00000624831.1
SMYD4	ENST00000954774.1		c.135-26C>T	intron	N/A	ENSP00000624833.1

Frequencies

GnomAD3 genomes

AF:

0.728

AC:

110726

AN:

151992

Hom.:

41255

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.666

AC:

161860

AN:

243138

AF XY:

0.670

show subpopulations

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 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.:

AF XY:

0.750

AC XY:

542196

AN XY:

722564

show subpopulations

African (AFR)

AF:

0.750

AC:

24555

AN:

32756

American (AMR)

AF:

0.421

AC:

17875

AN:

42446

Ashkenazi Jewish (ASJ)

AF:

0.692

AC:

17828

AN:

25764

East Asian (EAS)

AF:

0.487

AC:

19289

AN:

39636

South Asian (SAS)

AF:

0.536

AC:

45305

AN:

84520

European-Finnish (FIN)

AF:

0.681

AC:

36010

AN:

52890

Middle Eastern (MID)

AF:

0.677

AC:

3856

AN:

5698

European-Non Finnish (NFE)

AF:

0.802

AC:

889247

AN:

1108816

Other (OTH)

AF:

0.736

AC:

44106

AN:

59928

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

11195

22390

33585

44780

55975

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20546

41092

61638

82184

102730

<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:

0.728

AC:

110809

AN:

152110

Hom.:

41285

Cov.:

AF XY:

0.716

AC XY:

53213

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.752

AC:

31198

AN:

41496

American (AMR)

AF:

0.556

AC:

8492

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.699

AC:

2424

AN:

3468

East Asian (EAS)

AF:

0.473

AC:

2443

AN:

5170

South Asian (SAS)

AF:

0.520

AC:

2510

AN:

4826

European-Finnish (FIN)

AF:

0.666

AC:

7037

AN:

10566

Middle Eastern (MID)

AF:

0.724

AC:

213

AN:

294

European-Non Finnish (NFE)

AF:

0.797

AC:

54178

AN:

67998

Other (OTH)

AF:

0.713

AC:

1508

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1482

2965

4447

5930

7412

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

836

1672

2508

3344

4180

<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:

0.760

Hom.:

77099

Bravo

AF:

0.720

Asia WGS

AF:

0.468

AC:

1633

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.5

(source)

DANN

Benign

0.57

PhyloP100

-0.14

Mutation Taster

=16/84

disease causing

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over