12-121823550-G-T

Position:

• chr12-121823550-G-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001353345.2(SETD1B):​c.4971G>T​(p.Ala1657Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
• Consequence: SETD1B NM_001353345.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.77

Genes affected

SETD1B (HGNC:29187): (SET domain containing 1B, histone lysine methyltransferase) SET1B is a component of a histone methyltransferase complex that produces trimethylated histone H3 at Lys4 (Lee et al., 2007 [PubMed 17355966]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP7: Synonymous conserved (PhyloP=-4.77 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SETD1B	NM_001353345.2	c.4971G>T	p.Ala1657Ala	synonymous_variant	12/17	ENST00000604567.6	NP_001340274.1
SETD1B	XM_024448898.2	c.4971G>T	p.Ala1657Ala	synonymous_variant	12/17		XP_024304666.1
SETD1B	XM_047428552.1	c.4971G>T	p.Ala1657Ala	synonymous_variant	12/17		XP_047284508.1
SETD1B	XM_047428553.1	c.4971G>T	p.Ala1657Ala	synonymous_variant	12/17		XP_047284509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SETD1B	ENST00000604567.6	c.4971G>T	p.Ala1657Ala	synonymous_variant	12/17	5	NM_001353345.2	ENSP00000474253.1
SETD1B	ENST00000619791.1	c.4971G>T	p.Ala1657Ala	synonymous_variant	11/16	1		ENSP00000481531.1
SETD1B	ENST00000542440.5	c.4842G>T	p.Ala1614Ala	synonymous_variant	13/18	5		ENSP00000442924.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 59

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.010
DANN	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs3741593; hg19: chr12-122261456;