Variant chr12-121823550-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001353345.2(SETD1B):c.4971G>A(p.Ala1657Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 1,550,642 control chromosomes in the GnomAD database, including 211,876 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 15220 hom., cov: 30)

Exomes 𝑓: 0.52 ( 196656 hom. )

Consequence

SETD1B
NM_001353345.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -4.77

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 12-121823550-G-A is Benign according to our data. Variant chr12-121823550-G-A is described in ClinVar as [Benign]. Clinvar id is 1284001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.77 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SETD1B	ENST00000604567.6 linkuse as main transcript	c.4971G>A	p.Ala1657Ala	synonymous_variant	12/17	5	NM_001353345.2	ENSP00000474253.1	Q9UPS6-1
SETD1B	ENST00000619791.1 linkuse as main transcript	c.4971G>A	p.Ala1657Ala	synonymous_variant	11/16	1		ENSP00000481531.1	Q9UPS6-1
SETD1B	ENST00000542440.5 linkuse as main transcript	c.4842G>A	p.Ala1614Ala	synonymous_variant	13/18	5		ENSP00000442924.1	Q9UPS6-2

Frequencies

GnomAD3 genomes

AF:

0.407

AC:

61719

AN:

151724

Hom.:

15216

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.674

Gnomad AMR

AF:

0.466

Gnomad ASJ

AF:

0.617

Gnomad EAS

AF:

0.556

Gnomad SAS

AF:

0.470

Gnomad FIN

AF:

0.464

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.535

Gnomad OTH

AF:

0.449

GnomAD3 exomes

AF:

0.493

AC:

76576

AN:

155294

Hom.:

19781

AF XY:

0.497

AC XY:

40990

AN XY:

82486

show subpopulations

Gnomad AFR exome

AF:

0.0866

Gnomad AMR exome

AF:

0.462

Gnomad ASJ exome

AF:

0.616

Gnomad EAS exome

AF:

0.571

Gnomad SAS exome

AF:

0.463

Gnomad FIN exome

AF:

0.469

Gnomad NFE exome

AF:

0.543

Gnomad OTH exome

AF:

0.528

GnomAD4 exome

AF:

0.524

AC:

733166

AN:

1398800

Hom.:

196656

Cov.:

AF XY:

0.524

AC XY:

361266

AN XY:

689908

show subpopulations

Gnomad4 AFR exome

AF:

0.0862

Gnomad4 AMR exome

AF:

0.462

Gnomad4 ASJ exome

AF:

0.617

Gnomad4 EAS exome

AF:

0.544

Gnomad4 SAS exome

AF:

0.467

Gnomad4 FIN exome

AF:

0.465

Gnomad4 NFE exome

AF:

0.543

Gnomad4 OTH exome

AF:

0.514

GnomAD4 genome

AF:

0.406

AC:

61714

AN:

151842

Hom.:

15220

Cov.:

AF XY:

0.408

AC XY:

30274

AN XY:

74168

show subpopulations

Gnomad4 AFR

AF:

0.106

Gnomad4 AMR

AF:

0.465

Gnomad4 ASJ

AF:

0.617

Gnomad4 EAS

AF:

0.556

Gnomad4 SAS

AF:

0.470

Gnomad4 FIN

AF:

0.464

Gnomad4 NFE

AF:

0.535

Gnomad4 OTH

AF:

0.453

Alfa

AF:

0.494

Hom.:

14498

Bravo

AF:

0.397

Asia WGS

AF:

0.499

AC:

1735

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 22, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.011

DANN

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over