rs175041

Variant names:

• chr14-75003743-C-A
• rs175041
• NM_014239.4:c.433+44C>A

Your query was ambiguous. Multiple possible variants found:

• chr14-75003743-C-A
• chr14-75003743-C-G
• chr14-75003743-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014239.4(EIF2B2):​c.433+44C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.997 in 1,613,440 control chromosomes in the GnomAD database, including 802,330 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.99 (73977 hom., cov: 31)
  • Exomes 𝑓: 1.0 (728353 hom.)
• Consequence: EIF2B2 NM_014239.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.470
• Publications: 6 publications found

Genes affected

EIF2B2 (HGNC:3258): (eukaryotic translation initiation factor 2B subunit beta) This gene encodes the beta subunit of eukaryotic initiation factor-2B (EIF2B). EIF2B is involved in protein synthesis and exchanges GDP and GTP for its activation and deactivation. [provided by RefSeq, Aug 2011]

EIF2B2 Gene-Disease associations (from GenCC):

• leukoencephalopathy with vanishing white matter

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Illumina, Genomics England PanelApp
• leukoencephalopathy with vanishing white matter 2

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• leukoencephalopathy with vanishing white matter

  Inheritance: AR Classification: STRONG Submitted by: G2P
• leukoencephalopathy with vanishing white matter 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• ovarioleukodystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 14-75003743-C-A is Benign according to our data. Variant chr14-75003743-C-A is described in ClinVar as Benign. ClinVar VariationId is 260365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014239.4. 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
	EIF2B2	NM_014239.4	MANE Select	c.433+44C>A		intron	N/A	NP_055054.1	Q53XC2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF2B2	ENST00000266126.10	TSL:1 MANE Select	c.433+44C>A		intron	N/A	ENSP00000266126.5	P49770
	EIF2B2	ENST00000932124.1		c.433+44C>A		intron	N/A	ENSP00000602183.1
	EIF2B2	ENST00000932126.1		c.433+44C>A		intron	N/A	ENSP00000602185.1

Frequencies

GnomAD3 genomes AF: 0.985 AC: 149975 AN: 152200 Hom.: 73920 Cov.: 31

Gnomad AFR AF: 0.949

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.995

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.994

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.987

GnomAD2 exomes AF: 0.996 AC: 249119 AN: 250042 AF XY: 0.997

Gnomad AFR exome AF: 0.949

Gnomad AMR exome AF: 0.998

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.998

GnomAD4 exome AF: 0.998 AC: 1458863 AN: 1461122 Hom.: 728353 Cov.: 41 AF XY: 0.999 AC XY: 725842 AN XY: 726786

African (AFR) AF: 0.945 AC: 31645 AN: 33470

American (AMR) AF: 0.998 AC: 44463 AN: 44574

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26122 AN: 26122

East Asian (EAS) AF: 1.00 AC: 39695 AN: 39696

South Asian (SAS) AF: 1.00 AC: 86083 AN: 86102

European-Finnish (FIN) AF: 1.00 AC: 53386 AN: 53386

Middle Eastern (MID) AF: 0.997 AC: 5751 AN: 5768

European-Non Finnish (NFE) AF: 1.00 AC: 1111573 AN: 1111630

Other (OTH) AF: 0.996 AC: 60145 AN: 60374

GnomAD4 genome AF: 0.985 AC: 150091 AN: 152318 Hom.: 73977 Cov.: 31 AF XY: 0.986 AC XY: 73419 AN XY: 74476

African (AFR) AF: 0.949 AC: 39441 AN: 41552

American (AMR) AF: 0.995 AC: 15235 AN: 15310

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5178 AN: 5178

South Asian (SAS) AF: 1.00 AC: 4828 AN: 4830

European-Finnish (FIN) AF: 1.00 AC: 10616 AN: 10616

Middle Eastern (MID) AF: 0.993 AC: 292 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68033 AN: 68042

Other (OTH) AF: 0.987 AC: 2084 AN: 2112

Alfa AF: 0.996 Hom.: 83995

Bravo AF: 0.983

Asia WGS AF: 0.998 AC: 3472 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.6
DANN	Benign	0.79
PhyloP100		-0.47
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: rs175041; hg19: chr14-75470446;