22-37403148-G-T

Position:

• chr22-37403148-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELFN2	NM_052906.5	c.-463+14621C>A		intron_variant		ENST00000402918.7
ELFN2	NR_110512.2	n.182+24150C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELFN2	ENST00000402918.7	c.-463+14621C>A		intron_variant		4	NM_052906.5	P1
ELFN2	ENST00000452946.1	n.148+24150C>A		intron_variant, non_coding_transcript_variant		4

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

Gnomad4 AFR AF: 0.646

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.480

Gnomad4 EAS AF: 0.395

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.528

Gnomad4 NFE AF: 0.463

Gnomad4 OTH AF: 0.480

Alfa AF: 0.446 Hom.: 6394

Bravo AF: 0.504

Asia WGS AF: 0.358 AC: 1248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs4328731; hg19: chr22-37799188;