Genetic Variant SETD1A:c.-712C>T (chr16-30957268-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 ENST00000710314.1(SETD1A):c.-712C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 151,918 control chromosomes in the GnomAD database, including 23,474 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 0.53 ( 23458 hom., cov: 32)

Exomes 𝑓: 0.73 ( 16 hom. )

Consequence

SETD1A
ENST00000710314.1 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.01

Publications

24 publications found

Variant links:

Genes affected

SETD1A (HGNC:29010): (SET domain containing 1A, histone lysine methyltransferase) The protein encoded by this gene is a component of a histone methyltransferase (HMT) complex that produces mono-, di-, and trimethylated histone H3 at Lys4. Trimethylation of histone H3 at lysine 4 (H3K4me3) is a chromatin modification known to generally mark the transcription start sites of active genes. The protein contains SET domains, a RNA recognition motif domain and is a member of the class V-like SAM-binding methyltransferase superfamily. [provided by RefSeq, Dec 2016]

SETD1A Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
neurodevelopmental disorder with speech impairment and dysmorphic facies
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
epilepsy, early-onset, with or without developmental delay
Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

SETD1A links:

ENSG00000275263 (HGNC:):

ENSG00000275263 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000710314.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.74).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000710314.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SETD1A	ENST00000710314.1		c.-712C>T		upstream_gene	N/A	ENSP00000518195.1	O15047
	ENSG00000275263	ENST00000614997.1	TSL:6	n.-69G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.527

AC:

80025

AN:

151744

Hom.:

23444

Cov.:

show subpopulations

Gnomad AFR

AF:

0.272

Gnomad AMI

AF:

0.630

Gnomad AMR

AF:

0.570

Gnomad ASJ

AF:

0.691

Gnomad EAS

AF:

0.905

Gnomad SAS

AF:

0.308

Gnomad FIN

AF:

0.668

Gnomad MID

AF:

0.737

Gnomad NFE

AF:

0.626

Gnomad OTH

AF:

0.593

GnomAD4 exome

AF:

0.732

AC:

AN:

Hom.:

Cov.:

AF XY:

0.650

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.900

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.705

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

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:

0.527

AC:

80085

AN:

151862

Hom.:

23458

Cov.:

AF XY:

0.528

AC XY:

39223

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.272

AC:

11271

AN:

41390

American (AMR)

AF:

0.570

AC:

8690

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.691

AC:

2392

AN:

3462

East Asian (EAS)

AF:

0.905

AC:

4658

AN:

5146

South Asian (SAS)

AF:

0.310

AC:

1492

AN:

4808

European-Finnish (FIN)

AF:

0.668

AC:

7056

AN:

10562

Middle Eastern (MID)

AF:

0.741

AC:

218

AN:

294

European-Non Finnish (NFE)

AF:

0.626

AC:

42495

AN:

67932

Other (OTH)

AF:

0.589

AC:

1240

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

1670

3340

5011

6681

8351

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

674

1348

2022

2696

3370

<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:

0.576

Hom.:

6774

Bravo

AF:

0.518

Asia WGS

AF:

0.546

AC:

1902

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

1.0

(source)

DANN

Benign

0.95

PhyloP100

-1.0

PromoterAI

-0.051

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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