rs2592970

Positions:

• chr4-139534100-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.171-734G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 151,920 control chromosomes in the GnomAD database, including 35,862 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 0.68 (35862 hom., cov: 30)
• Consequence: SETD7 NM_030648.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08

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]

SETD7 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SETD7	NM_030648.4	c.171-734G>A		intron_variant		ENST00000274031.8	NP_085151.1
SETD7	NM_001306199.2	c.171-734G>A		intron_variant			NP_001293128.1
SETD7	NM_001306200.2	c.171-734G>A		intron_variant			NP_001293129.1
SETD7	NR_131339.2	n.354-734G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SETD7	ENST00000274031.8	c.171-734G>A		intron_variant		1	NM_030648.4	ENSP00000274031.3

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103615 AN: 151802 Hom.: 35830 Cov.: 30

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.734

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.668

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

GnomAD4 genome AF: 0.683 AC: 103698 AN: 151920 Hom.: 35862 Cov.: 30 AF XY: 0.681 AC XY: 50551 AN XY: 74204

Gnomad4 AFR AF: 0.796

Gnomad4 AMR AF: 0.734

Gnomad4 ASJ AF: 0.701

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.616

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.625

Gnomad4 OTH AF: 0.670

Alfa AF: 0.645 Hom.: 17483

Bravo AF: 0.698

Asia WGS AF: 0.598 AC: 2079 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.012
DANN	Benign	0.71

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: rs2592970; hg19: chr4-140455254;