rs2835267

Positions:

• chr21-36074727-T-C

Variant summary

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

The ENST00000399201.5(SETD4):​c.-203+4578A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 152,102 control chromosomes in the GnomAD database, including 30,652 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 0.63 (30652 hom., cov: 33)
• Consequence: SETD4 ENST00000399201.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730

Genes affected

SETD4 (HGNC:1258): (SET domain containing 4) Enables histone methyltransferase activity (H4-K20 specific). Involved in histone H4-K20 trimethylation. Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

CBR1-AS1 (HGNC:55777): (CBR1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBR1-AS1	NR_040084.1	n.377+154A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SETD4	ENST00000399201.5	c.-203+4578A>G		intron_variant		1		ENSP00000382152
CBR1-AS1	ENST00000535199.5	n.377+154A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95527 AN: 151982 Hom.: 30621 Cov.: 33

Gnomad AFR AF: 0.744

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.629 AC: 95615 AN: 152102 Hom.: 30652 Cov.: 33 AF XY: 0.630 AC XY: 46850 AN XY: 74346

Gnomad4 AFR AF: 0.745

Gnomad4 AMR AF: 0.604

Gnomad4 ASJ AF: 0.632

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.631

Gnomad4 FIN AF: 0.602

Gnomad4 NFE AF: 0.591

Gnomad4 OTH AF: 0.621

Alfa AF: 0.597 Hom.: 25736

Bravo AF: 0.632

Asia WGS AF: 0.479 AC: 1667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.8
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2835267; hg19: chr21-37447025;