12-121823550-G-T

Variant names:

• chr12-121823550-G-T
• rs3741593
• NM_001353345.2:c.4971G>T

Variant summary

Our verdict is Likely benign. The variant received -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. Synonymous variant affecting the same amino acid position (i.e. A1657A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: SETD1B NM_001353345.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.77
• Publications: 18 publications found

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]

SETD1B Gene-Disease associations (from GenCC):

• intellectual developmental disorder with seizures and language delay

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353345.2. 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
	SETD1B	NM_001353345.2	MANE Select	c.4971G>T	p.Ala1657Ala	synonymous	Exon 12 of 17	NP_001340274.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SETD1B	ENST00000604567.6	TSL:5 MANE Select	c.4971G>T	p.Ala1657Ala	synonymous	Exon 12 of 17	ENSP00000474253.1
	SETD1B	ENST00000619791.1	TSL:1	c.4971G>T	p.Ala1657Ala	synonymous	Exon 11 of 16	ENSP00000481531.1
	SETD1B	ENST00000542440.5	TSL:5	c.4842G>T	p.Ala1614Ala	synonymous	Exon 13 of 18	ENSP00000442924.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 59

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 18940

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.010
DANN	Benign	0.51
PhyloP100		-4.8
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

Other links and lift over

dbSNP: rs3741593; hg19: chr12-122261456;