rs743920

Variant names:

• chr22-29225139-C-G
• rs743920
• NM_133455.4:c.326C>G

Your query was ambiguous. Multiple possible variants found:

• chr22-29225139-C-G
• chr22-29225139-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_133455.4(EMID1):​c.326C>G​(p.Ala109Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,613,198 control chromosomes in the GnomAD database, including 45,963 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (12700 hom., cov: 34)
  • Exomes 𝑓: 0.17 (33263 hom.)
• Consequence: EMID1 NM_133455.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.443
• Publications: 23 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133455.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMID1	NM_133455.4	MANE Select	c.326C>G	p.Ala109Gly	missense	Exon 4 of 15	NP_597712.2
	EMID1	NM_001410828.1		c.326C>G	p.Ala109Gly	missense	Exon 4 of 15	NP_001397757.1
	EMID1	NM_001267895.2		c.320C>G	p.Ala107Gly	missense splice_region	Exon 4 of 15	NP_001254824.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMID1	ENST00000334018.11	TSL:1 MANE Select	c.326C>G	p.Ala109Gly	missense	Exon 4 of 15	ENSP00000335481.6
	EMID1	ENST00000404820.7	TSL:5	c.326C>G	p.Ala109Gly	missense	Exon 4 of 15	ENSP00000384452.3
	EMID1	ENST00000404755.7	TSL:5	c.326C>G	p.Ala109Gly	missense	Exon 4 of 14	ENSP00000385414.3

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48796 AN: 152086 Hom.: 12652 Cov.: 34

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.282

GnomAD2 exomes AF: 0.254 AC: 63613 AN: 250888 AF XY: 0.242

Gnomad AFR exome AF: 0.699

Gnomad AMR exome AF: 0.344

Gnomad ASJ exome AF: 0.195

Gnomad EAS exome AF: 0.603

Gnomad FIN exome AF: 0.110

Gnomad NFE exome AF: 0.125

Gnomad OTH exome AF: 0.199

GnomAD4 exome AF: 0.170 AC: 247885 AN: 1460994 Hom.: 33263 Cov.: 32 AF XY: 0.172 AC XY: 124658 AN XY: 726858

African (AFR) AF: 0.710 AC: 23749 AN: 33446

American (AMR) AF: 0.340 AC: 15218 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 5224 AN: 26104

East Asian (EAS) AF: 0.580 AC: 23018 AN: 39696

South Asian (SAS) AF: 0.310 AC: 26713 AN: 86230

European-Finnish (FIN) AF: 0.111 AC: 5921 AN: 53148

Middle Eastern (MID) AF: 0.207 AC: 1192 AN: 5764

European-Non Finnish (NFE) AF: 0.121 AC: 134374 AN: 1111534

Other (OTH) AF: 0.207 AC: 12476 AN: 60370

GnomAD4 genome AF: 0.321 AC: 48904 AN: 152204 Hom.: 12700 Cov.: 34 AF XY: 0.321 AC XY: 23881 AN XY: 74426

African (AFR) AF: 0.690 AC: 28644 AN: 41528

American (AMR) AF: 0.306 AC: 4670 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 684 AN: 3468

East Asian (EAS) AF: 0.609 AC: 3150 AN: 5172

South Asian (SAS) AF: 0.322 AC: 1556 AN: 4830

European-Finnish (FIN) AF: 0.105 AC: 1118 AN: 10620

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8361 AN: 67994

Other (OTH) AF: 0.288 AC: 609 AN: 2112

Alfa AF: 0.134 Hom.: 641

Bravo AF: 0.351

TwinsUK AF: 0.119 AC: 441

ALSPAC AF: 0.112 AC: 430

ESP6500AA AF: 0.679 AC: 2990

ESP6500EA AF: 0.129 AC: 1108

ExAC AF: 0.256 AC: 31053

Asia WGS AF: 0.454 AC: 1578 AN: 3478

EpiCase AF: 0.124

EpiControl AF: 0.131

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	14
DANN	Benign	0.10
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.093	T
MetaRNN	Benign	0.0000028	T
MetaSVM	Benign	-0.95	T
PhyloP100		0.44
PrimateAI	Benign	0.32	T
PROVEAN	Benign	1.5	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.092
MPC		0.12
ClinPred		0.000011	T
GERP RS		1.3
gMVP		0.23
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.35		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.35		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs743920; hg19: chr22-29621128; COSMIC: COSV61829081;