16-30957268-C-T

Variant names:

• chr16-30957268-C-T
• rs4889599
• ENST00000710314.1:c.-712C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 24 publications found

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 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: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000275263 (HGNC:):

ACMG classification

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SETD1A	ENST00000710314.1		c.-712C>T		upstream_gene	N/A	ENSP00000518195.1
	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.: 32

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: 41 AN: 56 Hom.: 16 Cov.: 0 AF XY: 0.650 AC XY: 26 AN XY: 40

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.900 AC: 9 AN: 10

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.705 AC: 31 AN: 44

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.527 AC: 80085 AN: 151862 Hom.: 23458 Cov.: 32 AF XY: 0.528 AC XY: 39223 AN XY: 74230

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

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
DANN	Benign	0.95
PhyloP100		-1.0
PromoterAI		-0.051	Neutral

Splicing

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

Other links and lift over

dbSNP: rs4889599; hg19: chr16-30968589;