4-139525951-A-C

Variant names:

• chr4-139525951-A-C
• rs7680948
• NM_030648.4:c.563-2516T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030648.4(SETD7):​c.563-2516T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,130 control chromosomes in the GnomAD database, including 6,973 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 0.30 (6973 hom., cov: 32)
• Consequence: SETD7 NM_030648.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.579
• Publications: 12 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SETD7	NM_030648.4	c.563-2516T>G		intron_variant	Intron 4 of 7	ENST00000274031.8	NP_085151.1
SETD7	NM_001306199.2	c.563-2516T>G		intron_variant	Intron 4 of 7		NP_001293128.1
SETD7	XM_017008661.1	c.149-2516T>G		intron_variant	Intron 2 of 5		XP_016864150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SETD7	ENST00000274031.8	c.563-2516T>G		intron_variant	Intron 4 of 7	1	NM_030648.4	ENSP00000274031.3
SETD7	ENST00000506866.7	c.563-2516T>G		intron_variant	Intron 4 of 7	1		ENSP00000427300.1

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45119 AN: 152012 Hom.: 6964 Cov.: 32

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.297 AC: 45164 AN: 152130 Hom.: 6973 Cov.: 32 AF XY: 0.296 AC XY: 22002 AN XY: 74358

African (AFR) AF: 0.354 AC: 14695 AN: 41462

American (AMR) AF: 0.285 AC: 4364 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 763 AN: 3470

East Asian (EAS) AF: 0.469 AC: 2429 AN: 5178

South Asian (SAS) AF: 0.285 AC: 1375 AN: 4826

European-Finnish (FIN) AF: 0.238 AC: 2517 AN: 10586

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18118 AN: 68006

Other (OTH) AF: 0.303 AC: 640 AN: 2110

Alfa AF: 0.277 Hom.: 7745

Bravo AF: 0.304

Asia WGS AF: 0.387 AC: 1345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.49
PhyloP100		-0.58
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: rs7680948; hg19: chr4-140447105;