NM_052906.5:c.-463+14621C>A

Variant names:

• chr22-37403148-G-T
• rs4328731
• NM_052906.5:c.-463+14621C>A

Variant summary

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

The NM_052906.5(ELFN2):​c.-463+14621C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 150,662 control chromosomes in the GnomAD database, including 19,918 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 0.50 (19918 hom., cov: 28)
• Consequence: ELFN2 NM_052906.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 6 publications found

Genes affected

ELFN2 (HGNC:29396): (extracellular leucine rich repeat and fibronectin type III domain containing 2) Predicted to enable protein phosphatase inhibitor activity. Predicted to be involved in negative regulation of catalytic activity. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ELFN2 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052906.5. 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
	ELFN2	NM_052906.5	MANE Select	c.-463+14621C>A		intron	N/A	NP_443138.2	Q5R3F8
	ELFN2	NR_110512.2		n.182+24150C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELFN2	ENST00000402918.7	TSL:4 MANE Select	c.-463+14621C>A		intron	N/A	ENSP00000385277.1	Q5R3F8
	ELFN2	ENST00000939364.1		c.-463+17136C>A		intron	N/A	ENSP00000609423.1
	ELFN2	ENST00000939365.1		c.-463+14621C>A		intron	N/A	ENSP00000609424.1

Frequencies

GnomAD3 genomes AF: 0.504 AC: 75803 AN: 150544 Hom.: 19911 Cov.: 28

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.528

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.503 AC: 75848 AN: 150662 Hom.: 19918 Cov.: 28 AF XY: 0.499 AC XY: 36714 AN XY: 73508

African (AFR) AF: 0.646 AC: 26397 AN: 40836

American (AMR) AF: 0.387 AC: 5866 AN: 15168

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1661 AN: 3462

East Asian (EAS) AF: 0.395 AC: 2014 AN: 5102

South Asian (SAS) AF: 0.318 AC: 1516 AN: 4766

European-Finnish (FIN) AF: 0.528 AC: 5409 AN: 10250

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.463 AC: 31393 AN: 67780

Other (OTH) AF: 0.480 AC: 1005 AN: 2094

Alfa AF: 0.454 Hom.: 8505

Bravo AF: 0.504

Asia WGS AF: 0.358 AC: 1248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.54
PhyloP100		-1.0
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: rs4328731; hg19: chr22-37799188;