dbSNP rs777278685: SETD1B:p.Pro7del (chr12-121804751-ACCC-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP3BS1BS2

The NM_001353345.2(SETD1B):c.20_22delCCC(p.Pro7del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000786 in 1,527,526 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000071 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SETD1B
NM_001353345.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.79

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
intellectual developmental disorder with seizures and language delay
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P

SETD1B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001353345.2

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0000713 (10/140262) while in subpopulation AMR AF = 0.000708 (10/14126). AF 95% confidence interval is 0.000384. There are 1 homozygotes in GnomAd4. There are 5 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 10 AD gene.

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.20_22delCCC	p.Pro7del	disruptive_inframe_deletion	Exon 2 of 17	NP_001340274.1	Q9UPS6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SETD1B	ENST00000604567.6	TSL:5 MANE Select	c.20_22delCCC	p.Pro7del	disruptive_inframe_deletion	Exon 2 of 17	ENSP00000474253.1	Q9UPS6-1
SETD1B	ENST00000619791.1	TSL:1	c.20_22delCCC	p.Pro7del	disruptive_inframe_deletion	Exon 1 of 16	ENSP00000481531.1	Q9UPS6-1
SETD1B	ENST00000542440.5	TSL:5	c.20_22delCCC	p.Pro7del	disruptive_inframe_deletion	Exon 2 of 18	ENSP00000442924.1	Q9UPS6-2

Frequencies

GnomAD3 genomes

AF:

0.0000713

AC:

AN:

140262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000708

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

GnomAD2 exomes

AF:

0.0000146

AC:

AN:

136830

AF XY:

0.0000137

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000922

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000144

AC:

AN:

1387264

Hom.:

AF XY:

0.00000146

AC XY:

AN XY:

684342

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31222

American (AMR)

AF:

0.0000572

AC:

AN:

34942

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24860

East Asian (EAS)

AF:

0.00

AC:

AN:

35382

South Asian (SAS)

AF:

0.00

AC:

AN:

78562

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5008

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1071472

Other (OTH)

AF:

0.00

AC:

AN:

57404

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000713

AC:

AN:

140262

Hom.:

Cov.:

AF XY:

0.0000736

AC XY:

AN XY:

67910

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

37048

American (AMR)

AF:

0.000708

AC:

AN:

14126

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3356

East Asian (EAS)

AF:

0.00

AC:

AN:

4752

South Asian (SAS)

AF:

0.00

AC:

AN:

4314

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9218

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

64392

Other (OTH)

AF:

0.00

AC:

AN:

1908

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.8

Mutation Taster

=77/23

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over