rs10118853

Variant names:

• chr9-108889742-C-A
• rs10118853
• NM_003640.5:c.3161-349G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-108889742-C-A
• chr9-108889742-C-T

Variant summary

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

The NM_003640.5(ELP1):​c.3161-349G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 356,194 control chromosomes in the GnomAD database, including 7,881 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 0.22 (4012 hom., cov: 32)
  • Exomes 𝑓: 0.19 (3869 hom.)
• Consequence: ELP1 NM_003640.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0440
• Publications: 5 publications found

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]

ELP1 Gene-Disease associations (from GenCC):

• primary dysautonomia

  Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women's Health
• Riley-Day syndrome

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• medulloblastoma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003640.5. 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
	ELP1	NM_003640.5	MANE Select	c.3161-349G>T		intron	N/A	NP_003631.2
	ELP1	NM_001318360.2		c.2819-349G>T		intron	N/A	NP_001305289.1	A0A6Q8PGW3
	ELP1	NM_001330749.2		c.2114-349G>T		intron	N/A	NP_001317678.1	F5H2T0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELP1	ENST00000374647.10	TSL:1 MANE Select	c.3161-349G>T		intron	N/A	ENSP00000363779.5	O95163
	ELP1	ENST00000537196.1	TSL:1	c.2114-349G>T		intron	N/A	ENSP00000439367.1	F5H2T0
	ELP1	ENST00000495759.6	TSL:1	n.*1771-349G>T		intron	N/A	ENSP00000433514.2	H0YDF3

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33040 AN: 151906 Hom.: 4009 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.199

GnomAD4 exome AF: 0.189 AC: 38678 AN: 204170 Hom.: 3869 AF XY: 0.193 AC XY: 21198 AN XY: 110102

African (AFR) AF: 0.329 AC: 1994 AN: 6070

American (AMR) AF: 0.157 AC: 1566 AN: 9992

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 1198 AN: 5290

East Asian (EAS) AF: 0.293 AC: 2800 AN: 9548

South Asian (SAS) AF: 0.219 AC: 7596 AN: 34724

European-Finnish (FIN) AF: 0.188 AC: 1735 AN: 9212

Middle Eastern (MID) AF: 0.173 AC: 132 AN: 762

European-Non Finnish (NFE) AF: 0.166 AC: 19618 AN: 117906

Other (OTH) AF: 0.191 AC: 2039 AN: 10666

GnomAD4 genome AF: 0.217 AC: 33063 AN: 152024 Hom.: 4012 Cov.: 32 AF XY: 0.218 AC XY: 16210 AN XY: 74314

African (AFR) AF: 0.319 AC: 13215 AN: 41440

American (AMR) AF: 0.160 AC: 2446 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 781 AN: 3468

East Asian (EAS) AF: 0.292 AC: 1504 AN: 5156

South Asian (SAS) AF: 0.229 AC: 1103 AN: 4822

European-Finnish (FIN) AF: 0.185 AC: 1949 AN: 10562

Middle Eastern (MID) AF: 0.212 AC: 62 AN: 292

European-Non Finnish (NFE) AF: 0.167 AC: 11337 AN: 67978

Other (OTH) AF: 0.198 AC: 418 AN: 2116

Alfa AF: 0.208 Hom.: 602

Bravo AF: 0.220

Asia WGS AF: 0.274 AC: 953 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.5
DANN	Benign	0.80
PhyloP100		0.044
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10118853;

hg19: chr9-111652022;