22-29225488-C-T

Variant names:

• chr22-29225488-C-T
• rs132390
• NM_133455.4:c.403+272C>T

Variant summary

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

The NM_133455.4(EMID1):​c.403+272C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.962 in 152,326 control chromosomes in the GnomAD database, including 70,545 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 0.96 (70545 hom., cov: 33)
• Consequence: EMID1 NM_133455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0220
• Publications: 64 publications found

Genes affected

EMID1 (HGNC:18036): (EMI domain containing 1) Predicted to be located in several cellular components, including Golgi apparatus; endoplasmic reticulum; and extracellular matrix. Predicted to be part of collagen trimer. [provided by Alliance of Genome Resources, Apr 2022]

LOC105372985 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMID1	NM_133455.4	c.403+272C>T		intron_variant	Intron 4 of 14	ENST00000334018.11	NP_597712.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EMID1	ENST00000334018.11	c.403+272C>T		intron_variant	Intron 4 of 14	1	NM_133455.4	ENSP00000335481.6

Frequencies

GnomAD3 genomes AF: 0.962 AC: 146484 AN: 152208 Hom.: 70496 Cov.: 33

Gnomad AFR AF: 0.944

Gnomad AMI AF: 0.905

Gnomad AMR AF: 0.982

Gnomad ASJ AF: 0.959

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.976

Gnomad FIN AF: 0.968

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.965

Gnomad OTH AF: 0.972

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

GnomAD4 genome AF: 0.962 AC: 146592 AN: 152326 Hom.: 70545 Cov.: 33 AF XY: 0.963 AC XY: 71760 AN XY: 74486

African (AFR) AF: 0.944 AC: 39238 AN: 41564

American (AMR) AF: 0.982 AC: 15025 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.959 AC: 3331 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5180 AN: 5182

South Asian (SAS) AF: 0.976 AC: 4715 AN: 4832

European-Finnish (FIN) AF: 0.968 AC: 10288 AN: 10626

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.965 AC: 65656 AN: 68024

Other (OTH) AF: 0.972 AC: 2057 AN: 2116

Alfa AF: 0.963 Hom.: 142688

Bravo AF: 0.962

Asia WGS AF: 0.986 AC: 3429 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	2.8
DANN	Benign	0.37
PhyloP100		0.022
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs132390; hg19: chr22-29621477;