9-108907977-C-T

Position:

• chr9-108907977-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003640.5(ELP1):​c.1460+328G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0904 in 152,238 control chromosomes in the GnomAD database, including 724 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 0.090 (724 hom., cov: 32)
• Consequence: ELP1 NM_003640.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.294

Genes affected

ELP1 (HGNC:5959): (elongator acetyltransferase complex subunit 1) The protein encoded by this gene is a scaffold protein and a regulator for three different kinases involved in proinflammatory signaling. The encoded protein can bind NF-kappa-B-inducing kinase and I-kappa-B kinases through separate domains and assemble them into an active kinase complex. Mutations in this gene have been associated with familial dysautonomia. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELP1	NM_003640.5	c.1460+328G>A		intron_variant		ENST00000374647.10	NP_003631.2
ELP1	NM_001318360.2	c.1118+328G>A		intron_variant			NP_001305289.1
ELP1	NM_001330749.2	c.413+328G>A		intron_variant			NP_001317678.1
ELP1	XM_047423991.1	c.1460+328G>A		intron_variant			XP_047279947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELP1	ENST00000374647.10	c.1460+328G>A		intron_variant		1	NM_003640.5	ENSP00000363779	P1

Frequencies

GnomAD3 genomes AF: 0.0903 AC: 13734 AN: 152120 Hom.: 719 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.0589

Gnomad ASJ AF: 0.0452

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.0644

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0720

Gnomad OTH AF: 0.0755

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

GnomAD4 genome AF: 0.0904 AC: 13757 AN: 152238 Hom.: 724 Cov.: 32 AF XY: 0.0907 AC XY: 6753 AN XY: 74430

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.0589

Gnomad4 ASJ AF: 0.0452

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.0644

Gnomad4 NFE AF: 0.0720

Gnomad4 OTH AF: 0.0756

Alfa AF: 0.0875 Hom.: 69

Bravo AF: 0.0914

Asia WGS AF: 0.146 AC: 509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.4
DANN	Benign	0.49

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

Other links and lift over

dbSNP: rs725036; hg19: chr9-111670257;