22-29231588-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_133455.4(EMID1):c.587-5C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00226 in 1,545,704 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (46 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (34 hom.)
• Consequence: EMID1 NM_133455.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.001176
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.156

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 22-29231588-C-G is Benign according to our data. Variant chr22-29231588-C-G is described in ClinVar as [Benign]. Clinvar id is 780636.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0121 (1841/152288) while in subpopulation AFR AF= 0.0423 (1759/41544). AF 95% confidence interval is 0.0407. There are 46 homozygotes in gnomad4. There are 860 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 46 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EMID1	NM_133455.4	c.587-5C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000334018.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EMID1	ENST00000334018.11	c.587-5C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_133455.4	P4

Frequencies

GnomAD3 genomes AF: 0.0121 AC: 1842 AN: 152170 Hom.: 46 Cov.: 32

Gnomad AFR AF: 0.0425

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00340

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.00275 AC: 406 AN: 147562 Hom.: 13 AF XY: 0.00189 AC XY: 147 AN XY: 77712

Gnomad AFR exome AF: 0.0415

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000357

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000110

Gnomad OTH exome AF: 0.000946

GnomAD4 exome AF: 0.00119 AC: 1657 AN: 1393416 Hom.: 34 Cov.: 31 AF XY: 0.00102 AC XY: 703 AN XY: 686788

Gnomad4 AFR exome AF: 0.0424

Gnomad4 AMR exome AF: 0.00167

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000280

Gnomad4 SAS exome AF: 0.0000894

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000772

Gnomad4 OTH exome AF: 0.00268

GnomAD4 genome AF: 0.0121 AC: 1841 AN: 152288 Hom.: 46 Cov.: 32 AF XY: 0.0116 AC XY: 860 AN XY: 74456

Gnomad4 AFR AF: 0.0423

Gnomad4 AMR AF: 0.00340

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00336 Hom.: 0

Bravo AF: 0.0143

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	3.5
Dann	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0012
dbscSNV1_RF	Benign	0.076
SpliceAI score (max)		0.040		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: rs78400471; hg19: chr22-29627577;