rs17050782

Positions:

• chr4-139501980-A-G

Variant summary

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

The NM_001306199.2(SETD7):​c.921-5459T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,126 control chromosomes in the GnomAD database, including 2,838 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 0.19 (2838 hom., cov: 32)
• Consequence: SETD7 NM_001306199.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SETD7	NM_001306199.2	c.921-5459T>C		intron_variant			NP_001293128.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SETD7	ENST00000506866.6	c.921-5459T>C		intron_variant		1		ENSP00000427300.1
SETD7	ENST00000515101.1	n.279-5459T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28228 AN: 152008 Hom.: 2836 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.186 AC: 28240 AN: 152126 Hom.: 2838 Cov.: 32 AF XY: 0.188 AC XY: 13985 AN XY: 74356

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.377

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.177

Alfa AF: 0.204 Hom.: 6603

Bravo AF: 0.175

Asia WGS AF: 0.218 AC: 756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.9
DANN	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17050782; hg19: chr4-140423134;