chr12-121804754-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001353345.2(SETD1B):​c.17C>A​(p.Pro6His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000122 in 1,550,056 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P6R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000097 ( 1 hom. )

Consequence

SETD1B
NM_001353345.2 missense

Scores

3
4
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.243
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.010497063).
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000349 (53/151898) while in subpopulation AFR AF= 0.00118 (49/41476). AF 95% confidence interval is 0.000918. There are 0 homozygotes in gnomad4. There are 27 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 53 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SETD1BNM_001353345.2 linkc.17C>A p.Pro6His missense_variant Exon 2 of 17 ENST00000604567.6 NP_001340274.1
SETD1BXM_024448898.2 linkc.17C>A p.Pro6His missense_variant Exon 2 of 17 XP_024304666.1
SETD1BXM_047428552.1 linkc.17C>A p.Pro6His missense_variant Exon 2 of 17 XP_047284508.1
SETD1BXM_047428553.1 linkc.17C>A p.Pro6His missense_variant Exon 2 of 17 XP_047284509.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SETD1BENST00000604567.6 linkc.17C>A p.Pro6His missense_variant Exon 2 of 17 5 NM_001353345.2 ENSP00000474253.1 Q9UPS6-1
SETD1BENST00000619791.1 linkc.17C>A p.Pro6His missense_variant Exon 1 of 16 1 ENSP00000481531.1 Q9UPS6-1
SETD1BENST00000542440.5 linkc.17C>A p.Pro6His missense_variant Exon 2 of 18 5 ENSP00000442924.1 Q9UPS6-2

Frequencies

GnomAD3 genomes
AF:
0.000343
AC:
52
AN:
151782
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00116
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000656
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:
0.0000442
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000151
AC:
23
AN:
152764
Hom.:
0
AF XY:
0.000173
AC XY:
14
AN XY:
81130
show subpopulations
Gnomad AFR exome
AF:
0.00203
Gnomad AMR exome
AF:
0.0000409
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000929
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000848
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000973
AC:
136
AN:
1398158
Hom.:
1
Cov.:
33
AF XY:
0.0000914
AC XY:
63
AN XY:
689602
show subpopulations
Gnomad4 AFR exome
AF:
0.00193
Gnomad4 AMR exome
AF:
0.0000282
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000280
Gnomad4 SAS exome
AF:
0.0000505
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000454
Gnomad4 OTH exome
AF:
0.000294
GnomAD4 genome
AF:
0.000349
AC:
53
AN:
151898
Hom.:
0
Cov.:
31
AF XY:
0.000364
AC XY:
27
AN XY:
74242
show subpopulations
Gnomad4 AFR
AF:
0.00118
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:
0.0000442
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000191
Hom.:
0
Bravo
AF:
0.000412
ExAC
AF:
0.000350
AC:
8

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.13
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0090
T;.;T;T
Eigen
Benign
-0.13
Eigen_PC
Benign
-0.11
FATHMM_MKL
Benign
0.66
D
LIST_S2
Benign
0.48
.;T;T;T
M_CAP
Pathogenic
0.75
D
MetaRNN
Benign
0.010
T;T;T;T
MetaSVM
Uncertain
-0.035
T
MutationAssessor
Benign
1.5
L;L;.;L
PrimateAI
Pathogenic
0.79
T
PROVEAN
Benign
-1.9
.;N;N;.
REVEL
Uncertain
0.32
Sift
Uncertain
0.0020
.;D;D;.
Sift4G
Pathogenic
0.0
D;D;D;D
Polyphen
0.94
P;.;.;P
Vest4
0.18
MVP
0.78
MPC
2.7
ClinPred
0.10
T
GERP RS
1.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.12
gMVP
0.43

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.

Other links and lift over

dbSNP: rs553235589; hg19: chr12-122242660; API