rs2592970

Variant names:

• chr4-139534100-C-T
• rs2592970
• NM_030648.4:c.171-734G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030648.4. 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
	SETD7	NM_030648.4	MANE Select	c.171-734G>A		intron	N/A	NP_085151.1
	SETD7	NM_001306199.2		c.171-734G>A		intron	N/A	NP_001293128.1
	SETD7	NM_001306200.2		c.171-734G>A		intron	N/A	NP_001293129.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SETD7	ENST00000274031.8	TSL:1 MANE Select	c.171-734G>A		intron	N/A	ENSP00000274031.3
	SETD7	ENST00000506866.7	TSL:1	c.171-734G>A		intron	N/A	ENSP00000427300.1
	SETD7	ENST00000406354.1	TSL:1	n.343-734G>A		intron	N/A

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

African (AFR) AF: 0.796 AC: 33014 AN: 41450

American (AMR) AF: 0.734 AC: 11193 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 2428 AN: 3464

East Asian (EAS) AF: 0.555 AC: 2861 AN: 5154

South Asian (SAS) AF: 0.616 AC: 2966 AN: 4816

European-Finnish (FIN) AF: 0.607 AC: 6390 AN: 10528

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.625 AC: 42499 AN: 67954

Other (OTH) AF: 0.670 AC: 1414 AN: 2110

Alfa AF: 0.646 Hom.: 23786

Bravo AF: 0.698

Asia WGS AF: 0.598 AC: 2079 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.012
DANN	Benign	0.71
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2592970; hg19: chr4-140455254;