Variant 12-121804732-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6

The NM_001353345.2(SETD1B):c.-6A>G variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000129 in 1,549,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

SETD1B
NM_001353345.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.81

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 Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 12-121804732-A-G is Benign according to our data. Variant chr12-121804732-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3053007.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SETD1B	NM_001353345.2 linkuse as main transcript	c.-6A>G		5_prime_UTR_premature_start_codon_gain_variant	2/17	ENST00000604567.6	NP_001340274.1
SETD1B	NM_001353345.2 linkuse as main transcript	c.-6A>G		5_prime_UTR_variant	2/17	ENST00000604567.6	NP_001340274.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SETD1B	ENST00000604567 linkuse as main transcript	c.-6A>G	5_prime_UTR_premature_start_codon_gain_variant	2/17	5	NM_001353345.2	ENSP00000474253.1	Q9UPS6-1
SETD1B	ENST00000542440 linkuse as main transcript	c.-6A>G	5_prime_UTR_premature_start_codon_gain_variant	2/18	5		ENSP00000442924.1	Q9UPS6-2
SETD1B	ENST00000604567 linkuse as main transcript	c.-6A>G	5_prime_UTR_variant	2/17	5	NM_001353345.2	ENSP00000474253.1	Q9UPS6-1
SETD1B	ENST00000542440 linkuse as main transcript	c.-6A>G	5_prime_UTR_variant	2/18	5		ENSP00000442924.1	Q9UPS6-2

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151640

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.16e-7

AC:

AN:

1397494

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689260

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.27e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151640

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74036

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SETD1B-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 05, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.86

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

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