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

Variant summary

Our verdict is Benign. Variant got -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

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 -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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
SETD1B	NM_001353345.2 link	c.20_22delCCC	p.Pro7del	disruptive_inframe_deletion	Exon 2 of 17	ENST00000604567.6	NP_001340274.1
SETD1B	XM_024448898.2 link	c.20_22delCCC	p.Pro7del	disruptive_inframe_deletion	Exon 2 of 17		XP_024304666.1
SETD1B	XM_047428552.1 link	c.20_22delCCC	p.Pro7del	disruptive_inframe_deletion	Exon 2 of 17		XP_047284508.1
SETD1B	XM_047428553.1 link	c.20_22delCCC	p.Pro7del	disruptive_inframe_deletion	Exon 2 of 17		XP_047284509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SETD1B	ENST00000604567.6 link	c.20_22delCCC	p.Pro7del	disruptive_inframe_deletion	Exon 2 of 17	5	NM_001353345.2	ENSP00000474253.1	Q9UPS6-1
SETD1B	ENST00000619791.1 link	c.20_22delCCC	p.Pro7del	disruptive_inframe_deletion	Exon 1 of 16	1		ENSP00000481531.1	Q9UPS6-1
SETD1B	ENST00000542440.5 link	c.20_22delCCC	p.Pro7del	disruptive_inframe_deletion	Exon 2 of 18	5		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

GnomAD3 exomes

AF:

0.0000146

AC:

AN:

136830

Hom.:

AF XY:

0.0000137

AC XY:

AN XY:

72846

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 SAS 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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000572

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000713

AC:

AN:

140262

Hom.:

Cov.:

AF XY:

0.0000736

AC XY:

AN XY:

67910

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000708

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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