Variant 12-121804759-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001353345.2(SETD1B):c.22C>A(p.His8Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000776 in 1,546,644 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.0000079 ( 1 hom. )

Consequence

SETD1B
NM_001353345.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.80

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.23138285).

BS2

High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SETD1B	NM_001353345.2 link	c.22C>A	p.His8Asn	missense_variant	2/17	ENST00000604567.6	NP_001340274.1
SETD1B	XM_024448898.2 link	c.22C>A	p.His8Asn	missense_variant	2/17		XP_024304666.1
SETD1B	XM_047428552.1 link	c.22C>A	p.His8Asn	missense_variant	2/17		XP_047284508.1
SETD1B	XM_047428553.1 link	c.22C>A	p.His8Asn	missense_variant	2/17		XP_047284509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SETD1B	ENST00000604567.6 link	c.22C>A	p.His8Asn	missense_variant	2/17	5	NM_001353345.2	ENSP00000474253.1	Q9UPS6-1
SETD1B	ENST00000619791.1 link	c.22C>A	p.His8Asn	missense_variant	1/16	1		ENSP00000481531.1	Q9UPS6-1
SETD1B	ENST00000542440.5 link	c.22C>A	p.His8Asn	missense_variant	2/18	5		ENSP00000442924.1	Q9UPS6-2

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151756

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000397

AC:

AN:

151156

Hom.:

AF XY:

0.0000125

AC XY:

AN XY:

80290

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000207

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000172

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000789

AC:

AN:

1394888

Hom.:

Cov.:

AF XY:

0.00000581

AC XY:

AN XY:

688018

show subpopulations

Gnomad4 AFR exome

AF:

0.0000319

Gnomad4 AMR exome

AF:

0.000142

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000254

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000279

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151756

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74092

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Benign

0.95

DEOGEN2

Benign

0.0083

T;.;T;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.49

.;T;T;T

M_CAP

Pathogenic

0.83

MetaRNN

Benign

0.23

T;T;T;T

MetaSVM

Benign

-0.30

MutationAssessor

Benign

1.1

L;L;.;L

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.2

.;N;N;.

REVEL

Uncertain

0.34

Sift

Uncertain

0.0090

.;D;D;.

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.33

B;.;.;B

Vest4

0.31

MutPred

0.098

Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);

MVP

0.67

MPC

2.0

ClinPred

0.11

GERP RS

2.1

Varity_R

0.13

gMVP

0.47

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over