12-92836413-T-C

Variant names:

• chr12-92836413-T-C
• rs2120576
• NM_003566.4:c.916-3563A>G

Variant summary

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

The NM_003566.4(EEA1):​c.916-3563A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,204 control chromosomes in the GnomAD database, including 1,998 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 0.12 (1998 hom., cov: 31)
• Consequence: EEA1 NM_003566.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263
• Publications: 4 publications found

Genes affected

EEA1 (HGNC:3185): (early endosome antigen 1) Enables 1-phosphatidylinositol binding activity; GTP-dependent protein binding activity; and protein homodimerization activity. Involved in endocytosis; vesicle fusion; and viral RNA genome replication. Located in cytosol and early endosome. Is extrinsic component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EEA1	NM_003566.4	c.916-3563A>G		intron_variant	Intron 10 of 28	ENST00000322349.13	NP_003557.3
EEA1	XM_011538814.3	c.1042-3563A>G		intron_variant	Intron 11 of 29		XP_011537116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EEA1	ENST00000322349.13	c.916-3563A>G		intron_variant	Intron 10 of 28	1	NM_003566.4	ENSP00000317955.8
EEA1	ENST00000418984.7	n.*665-3563A>G		intron_variant	Intron 9 of 17	5		ENSP00000394312.3

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18303 AN: 152086 Hom.: 1990 Cov.: 31

Gnomad AFR AF: 0.0293

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.120 AC: 18314 AN: 152204 Hom.: 1998 Cov.: 31 AF XY: 0.127 AC XY: 9435 AN XY: 74386

African (AFR) AF: 0.0292 AC: 1215 AN: 41562

American (AMR) AF: 0.304 AC: 4638 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 470 AN: 3470

East Asian (EAS) AF: 0.484 AC: 2502 AN: 5172

South Asian (SAS) AF: 0.122 AC: 588 AN: 4820

European-Finnish (FIN) AF: 0.127 AC: 1340 AN: 10584

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7180 AN: 68008

Other (OTH) AF: 0.133 AC: 281 AN: 2108

Alfa AF: 0.119 Hom.: 2992

Bravo AF: 0.135

Asia WGS AF: 0.285 AC: 987 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.50
PhyloP100		-0.26
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: rs2120576; hg19: chr12-93230189;