rs1075650

Variant names:

• chr9-129176634-T-C
• rs1075650
• NM_203434.3:c.*204A>G

Variant summary

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

The NM_203434.3(IER5L):​c.*204A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 661,754 control chromosomes in the GnomAD database, including 26,158 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 0.25 (4911 hom., cov: 32)
  • Exomes 𝑓: 0.28 (21247 hom.)
• Consequence: IER5L NM_203434.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.94
• Publications: 20 publications found

Genes affected

IER5L (HGNC:23679): (immediate early response 5 like)

ENSG00000235007 (HGNC:):

IER5L-AS1 (HGNC:55825): (IER5L antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IER5L	NM_203434.3	c.*204A>G		3_prime_UTR_variant	Exon 1 of 1	ENST00000372491.4	NP_982258.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IER5L	ENST00000372491.4	c.*204A>G		3_prime_UTR_variant	Exon 1 of 1	6	NM_203434.3	ENSP00000361569.2
ENSG00000235007	ENST00000674648.1	c.109-32235T>C		intron_variant	Intron 2 of 2			ENSP00000502744.1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37383 AN: 151910 Hom.: 4908 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.292

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.257

GnomAD4 exome AF: 0.282 AC: 143590 AN: 509732 Hom.: 21247 Cov.: 8 AF XY: 0.281 AC XY: 71566 AN XY: 254698

African (AFR) AF: 0.157 AC: 1778 AN: 11292

American (AMR) AF: 0.191 AC: 1666 AN: 8702

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 2785 AN: 11552

East Asian (EAS) AF: 0.114 AC: 2657 AN: 23294

South Asian (SAS) AF: 0.242 AC: 5150 AN: 21276

European-Finnish (FIN) AF: 0.240 AC: 5546 AN: 23144

Middle Eastern (MID) AF: 0.262 AC: 504 AN: 1922

European-Non Finnish (NFE) AF: 0.304 AC: 116405 AN: 382982

Other (OTH) AF: 0.278 AC: 7099 AN: 25568

GnomAD4 genome AF: 0.246 AC: 37403 AN: 152022 Hom.: 4911 Cov.: 32 AF XY: 0.241 AC XY: 17886 AN XY: 74324

African (AFR) AF: 0.167 AC: 6944 AN: 41472

American (AMR) AF: 0.231 AC: 3530 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 881 AN: 3470

East Asian (EAS) AF: 0.168 AC: 869 AN: 5174

South Asian (SAS) AF: 0.245 AC: 1178 AN: 4816

European-Finnish (FIN) AF: 0.228 AC: 2401 AN: 10550

Middle Eastern (MID) AF: 0.300 AC: 87 AN: 290

European-Non Finnish (NFE) AF: 0.303 AC: 20580 AN: 67938

Other (OTH) AF: 0.256 AC: 542 AN: 2114

Alfa AF: 0.285 Hom.: 10000

Bravo AF: 0.240

Asia WGS AF: 0.224 AC: 776 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Benign	0.88
PhyloP100		2.9
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: rs1075650; hg19: chr9-131938913;