rs11640961

Variant names:

• chr16-30968497-C-T
• rs11640961
• NM_014712.3:c.2771-808C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014712.3(SETD1A):​c.2771-808C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 151,120 control chromosomes in the GnomAD database, including 10,694 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.

• Frequency: Genomes: 𝑓 0.33 (10694 hom., cov: 29)
• Consequence: SETD1A NM_014712.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.998
• Publications: 15 publications found

Genes affected

SETD1A (HGNC:29010): (SET domain containing 1A, histone lysine methyltransferase) The protein encoded by this gene is a component of a histone methyltransferase (HMT) complex that produces mono-, di-, and trimethylated histone H3 at Lys4. Trimethylation of histone H3 at lysine 4 (H3K4me3) is a chromatin modification known to generally mark the transcription start sites of active genes. The protein contains SET domains, a RNA recognition motif domain and is a member of the class V-like SAM-binding methyltransferase superfamily. [provided by RefSeq, Dec 2016]

SETD1A Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with speech impairment and dysmorphic facies

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• epilepsy, early-onset, with or without developmental delay

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SETD1A	NM_014712.3	c.2771-808C>T		intron_variant	Intron 10 of 18	ENST00000262519.14	NP_055527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SETD1A	ENST00000262519.14	c.2771-808C>T		intron_variant	Intron 10 of 18	1	NM_014712.3	ENSP00000262519.8
SETD1A	ENST00000684162.1	c.2771-808C>T		intron_variant	Intron 10 of 18			ENSP00000507683.1
SETD1A	ENST00000710314.1	c.2771-808C>T		intron_variant	Intron 10 of 18			ENSP00000518195.1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49441 AN: 151008 Hom.: 10693 Cov.: 29

Gnomad AFR AF: 0.0759

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.902

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.397

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.327 AC: 49441 AN: 151120 Hom.: 10694 Cov.: 29 AF XY: 0.329 AC XY: 24255 AN XY: 73662

African (AFR) AF: 0.0757 AC: 3120 AN: 41236

American (AMR) AF: 0.399 AC: 6047 AN: 15146

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1849 AN: 3466

East Asian (EAS) AF: 0.902 AC: 4626 AN: 5126

South Asian (SAS) AF: 0.200 AC: 961 AN: 4806

European-Finnish (FIN) AF: 0.428 AC: 4356 AN: 10184

Middle Eastern (MID) AF: 0.517 AC: 150 AN: 290

European-Non Finnish (NFE) AF: 0.399 AC: 27107 AN: 67864

Other (OTH) AF: 0.394 AC: 826 AN: 2094

Alfa AF: 0.392 Hom.: 10440

Bravo AF: 0.327

Asia WGS AF: 0.473 AC: 1647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.20
DANN	Benign	0.21
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11640961; hg19: chr16-30979818;