4-139530933-C-T

Variant names:

• chr4-139530933-C-T
• rs11100112
• NM_030648.4:c.373-1713G>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.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
• Publications: 3 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.478 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.373-1713G>A		intron	N/A	NP_085151.1	Q8WTS6
	SETD7	NM_001306199.2		c.373-1713G>A		intron	N/A	NP_001293128.1	D6RJA0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SETD7	ENST00000274031.8	TSL:1 MANE Select	c.373-1713G>A		intron	N/A	ENSP00000274031.3	Q8WTS6
	SETD7	ENST00000506866.7	TSL:1	c.373-1713G>A		intron	N/A	ENSP00000427300.1	D6RJA0
	SETD7	ENST00000954984.1		c.373-1713G>A		intron	N/A	ENSP00000625043.1

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

African (AFR) AF: 0.483 AC: 20012 AN: 41420

American (AMR) AF: 0.283 AC: 4323 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 682 AN: 3468

East Asian (EAS) AF: 0.490 AC: 2531 AN: 5168

South Asian (SAS) AF: 0.257 AC: 1238 AN: 4816

European-Finnish (FIN) AF: 0.192 AC: 2025 AN: 10552

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14909 AN: 67968

Other (OTH) AF: 0.306 AC: 645 AN: 2110

Alfa AF: 0.267 Hom.: 4700

Bravo AF: 0.322

Asia WGS AF: 0.391 AC: 1359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.3
DANN	Benign	0.70
PhyloP100		-0.38
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: rs11100112; hg19: chr4-140452087;