rs2054213

Variant names:

• chr16-30960489-A-C
• rs2054213
• NM_014712.3:c.247-778A>C

Your query was ambiguous. Multiple possible variants found:

• chr16-30960489-A-C
• chr16-30960489-A-G
• chr16-30960489-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014712.3(SETD1A):​c.247-778A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: SETD1A NM_014712.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.827
• Publications: 25 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SETD1A	NM_014712.3	c.247-778A>C		intron_variant	Intron 3 of 18	ENST00000262519.14	NP_055527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SETD1A	ENST00000262519.14	c.247-778A>C		intron_variant	Intron 3 of 18	1	NM_014712.3	ENSP00000262519.8
SETD1A	ENST00000684162.1	c.247-778A>C		intron_variant	Intron 3 of 18			ENSP00000507683.1
SETD1A	ENST00000710314.1	c.247-778A>C		intron_variant	Intron 3 of 18			ENSP00000518195.1
SETD1A	ENST00000682768.1	c.247-778A>C		intron_variant	Intron 3 of 5			ENSP00000508271.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.50
DANN	Benign	0.59
PhyloP100		-0.83

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: rs2054213; hg19: chr16-30971810;