4-139530933-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030648.4(SETD7):c.373-1713G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 151,970 control chromosomes in the GnomAD database, including 8,284 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 0.31 (8284 hom., cov: 32)
• Consequence: SETD7 NM_030648.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.384

Genes affected

SETD7 (HGNC:30412): (SET domain containing 7, histone lysine methyltransferase) Enables histone-lysine N-methyltransferase activity and p53 binding activity. Involved in peptidyl-lysine dimethylation and peptidyl-lysine monomethylation. Acts upstream of or within cellular response to DNA damage stimulus and heterochromatin organization. Located in chromosome and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SETD7	NM_030648.4	c.373-1713G>A		intron_variant		ENST00000274031.8
SETD7	NM_001306199.2	c.373-1713G>A		intron_variant
SETD7	XM_017008661.1	c.-56-1699G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SETD7	ENST00000274031.8	c.373-1713G>A		intron_variant		1	NM_030648.4	P1
SETD7	ENST00000506866.6	c.373-1713G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46540 AN: 151852 Hom.: 8264 Cov.: 32

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.306

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.307 AC: 46609 AN: 151970 Hom.: 8284 Cov.: 32 AF XY: 0.307 AC XY: 22780 AN XY: 74278

Gnomad4 AFR AF: 0.483

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.490

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.306

Alfa AF: 0.264 Hom.: 2332

Bravo AF: 0.322

Asia WGS AF: 0.391 AC: 1359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	2.3
Dann	Benign	0.70

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

LitVar

Other links and lift over

dbSNP: rs11100112; hg19: chr4-140452087;