16-30957268-C-T

Position:

• chr16-30957268-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SETD1A	ENST00000710314.1	c.-712C>T		upstream_gene_variant				ENSP00000518195.1

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

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.900

Gnomad4 NFE exome AF: 0.705

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

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.691

Gnomad4 EAS AF: 0.905

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.668

Gnomad4 NFE AF: 0.626

Gnomad4 OTH AF: 0.589

Alfa AF: 0.582 Hom.: 6746

Bravo AF: 0.518

Asia WGS AF: 0.546 AC: 1902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.0
DANN	Benign	0.95

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4889599; hg19: chr16-30968589;