4-139547024-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_030648.4(SETD7):c.66G>A(p.Pro22=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00233 in 1,614,016 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (41 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (46 hom.)
• Consequence: SETD7 NM_030648.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.05

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

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001744777).
• BP6: Variant 4-139547024-C-T is Benign according to our data. Variant chr4-139547024-C-T is described in ClinVar as [Benign]. Clinvar id is 786048.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.05 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.012 (1831/152150) while in subpopulation AFR AF= 0.0419 (1741/41510). AF 95% confidence interval is 0.0403. There are 41 homozygotes in gnomad4. There are 835 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1828 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SETD7	NM_030648.4	c.66G>A	p.Pro22=	synonymous_variant	2/8	ENST00000274031.8
SETD7	NM_001306199.2	c.66G>A	p.Pro22=	synonymous_variant	2/8
SETD7	NM_001306200.2	c.66G>A	p.Pro22=	synonymous_variant	2/3
SETD7	NR_131339.2	n.249G>A		non_coding_transcript_exon_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SETD7	ENST00000274031.8	c.66G>A	p.Pro22=	synonymous_variant	2/8	1	NM_030648.4	P1

Frequencies

GnomAD3 genomes AF: 0.0120 AC: 1828 AN: 152032 Hom.: 41 Cov.: 32

Gnomad AFR AF: 0.0420

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00452

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00718

GnomAD3 exomes AF: 0.00329 AC: 827 AN: 251420 Hom.: 14 AF XY: 0.00233 AC XY: 316 AN XY: 135888

Gnomad AFR exome AF: 0.0437

Gnomad AMR exome AF: 0.00208

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00277

GnomAD4 exome AF: 0.00132 AC: 1927 AN: 1461866 Hom.: 46 Cov.: 31 AF XY: 0.00115 AC XY: 833 AN XY: 727234

Gnomad4 AFR exome AF: 0.0449

Gnomad4 AMR exome AF: 0.00253

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.000638

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000216

Gnomad4 OTH exome AF: 0.00356

GnomAD4 genome AF: 0.0120 AC: 1831 AN: 152150 Hom.: 41 Cov.: 32 AF XY: 0.0112 AC XY: 835 AN XY: 74384

Gnomad4 AFR AF: 0.0419

Gnomad4 AMR AF: 0.00451

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00711

Alfa AF: 0.00605 Hom.: 11

Bravo AF: 0.0137

ESP6500AA AF: 0.0404 AC: 178

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00385 AC: 468

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.67
Cadd	Benign	3.5
Dann	Benign	0.87
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.015	N
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	D;D;D;N
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.026
Vest4		0.17
MVP		0.085
ClinPred		0.055	T
GERP RS		-11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs35955363; hg19: chr4-140468178; COSMIC: COSV99064633; COSMIC: COSV99064633;