14-52658016-A-C

Variant names:

• chr14-52658016-A-C
• rs114268892
• NM_014584.3:c.716-7T>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_014584.3(ERO1A):​c.716-7T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000483 in 1,590,650 control chromosomes in the GnomAD database, including 6 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 0.0026 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00026 (4 hom.)
• Consequence: ERO1A NM_014584.3 splice_region, intron
• Scores: Splicing: ADA: 0.00001055
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0450
• Publications: 0 publications found

Genes affected

ERO1A (HGNC:13280): (endoplasmic reticulum oxidoreductase 1 alpha) Enables oxidoreductase activity. Involved in chaperone cofactor-dependent protein refolding. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006106645).
• BP6: Variant 14-52658016-A-C is Benign according to our data. Variant chr14-52658016-A-C is described in ClinVar as Benign. ClinVar VariationId is 716384.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014584.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERO1A	NM_014584.3	MANE Select	c.716-7T>G		splice_region intron	N/A	NP_055399.1	Q96HE7
	ERO1A	NM_001382464.1		c.755-7T>G		splice_region intron	N/A	NP_001369393.1
	ERO1A	NM_001382465.1		c.704-7T>G		splice_region intron	N/A	NP_001369394.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERO1A	ENST00000395686.8	TSL:1 MANE Select	c.716-7T>G		splice_region intron	N/A	ENSP00000379042.3	Q96HE7
	ERO1A	ENST00000629528.2	TSL:5	c.707T>G	p.Phe236Cys	missense	Exon 9 of 9	ENSP00000487101.1	G3V3E6
	ERO1A	ENST00000964628.1		c.755-7T>G		splice_region intron	N/A	ENSP00000634687.1

Frequencies

GnomAD3 genomes AF: 0.00257 AC: 391 AN: 152062 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00908

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000672 AC: 164 AN: 244064 AF XY: 0.000425

Gnomad AFR exome AF: 0.00945

Gnomad AMR exome AF: 0.000184

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000268

Gnomad OTH exome AF: 0.000334

GnomAD4 exome AF: 0.000263 AC: 379 AN: 1438468 Hom.: 4 Cov.: 26 AF XY: 0.000229 AC XY: 164 AN XY: 716448

African (AFR) AF: 0.00972 AC: 318 AN: 32716

American (AMR) AF: 0.000209 AC: 9 AN: 43050

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25878

East Asian (EAS) AF: 0.00 AC: 0 AN: 39460

South Asian (SAS) AF: 0.0000239 AC: 2 AN: 83560

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.000349 AC: 2 AN: 5728

European-Non Finnish (NFE) AF: 0.0000155 AC: 17 AN: 1095096

Other (OTH) AF: 0.000520 AC: 31 AN: 59608

GnomAD4 genome AF: 0.00256 AC: 390 AN: 152182 Hom.: 2 Cov.: 32 AF XY: 0.00227 AC XY: 169 AN XY: 74414

African (AFR) AF: 0.00905 AC: 375 AN: 41442

American (AMR) AF: 0.000784 AC: 12 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68008

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00135 Hom.: 0

Bravo AF: 0.00314

ESP6500AA AF: 0.0107 AC: 47

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000840 AC: 102

Asia WGS AF: 0.000578 AC: 2 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	12
DANN	Benign	0.96
DEOGEN2	Benign	0.11	T
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.32	T
MetaRNN	Benign	0.0061	T
PhyloP100		0.045
Sift4G	Uncertain	0.016	D
Vest4		0.15
MVP		0.18
GERP RS		-2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000011
dbscSNV1_RF	Benign	0.042
SpliceAI score (max)		0.060		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: rs114268892; hg19: chr14-53124734;