X-13596999-A-G

Position:

• chrX-13596999-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015507.4(EGFL6):​c.280+2071A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 110,992 control chromosomes in the GnomAD database, including 14,720 homozygotes. There are 18,422 hemizygotes in GnomAD. 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 0.56 (14720 hom., 18422 hem., cov: 23)
• Consequence: EGFL6 NM_015507.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109

Genes affected

EGFL6 (HGNC:3235): (EGF like domain multiple 6) This gene encodes a member of the epidermal growth factor (EGF) repeat superfamily. Members of this superfamily are characterized by the presence of EGF-like repeats and are often involved in the regulation of cell cycle, proliferation, and developmental processes. The gene product contains a signal peptide, suggesting that it is secreted; an EGF repeat region consisting of 4 complete EGF-like repeats and 1 partial EGF-like repeat, 3 of which have a calcium-binding consensus sequence; an arg-gly-asp integrin association motif; and a MAM domain, which is believed to have an adhesive function. This gene is expressed early during development, and its expression has been detected in lung and meningioma tumors. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFL6	NM_015507.4	c.280+2071A>G		intron_variant		ENST00000361306.6	NP_056322.2
EGFL6	NM_001167890.2	c.280+2071A>G		intron_variant			NP_001161362.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFL6	ENST00000361306.6	c.280+2071A>G		intron_variant		1	NM_015507.4	ENSP00000355126.1
EGFL6	ENST00000380602.3	c.280+2071A>G		intron_variant		1		ENSP00000369976.3

Frequencies

GnomAD3 genomes AF: 0.564 AC: 62561 AN: 110936 Hom.: 14705 Cov.: 23 AF XY: 0.554 AC XY: 18368 AN XY: 33140

Gnomad AFR AF: 0.902

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.564 AC: 62634 AN: 110992 Hom.: 14720 Cov.: 23 AF XY: 0.555 AC XY: 18422 AN XY: 33206

Gnomad4 AFR AF: 0.902

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.809

Gnomad4 SAS AF: 0.743

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.381

Gnomad4 OTH AF: 0.549

Alfa AF: 0.423 Hom.: 34605

Bravo AF: 0.597

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	0.45

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: rs5978649; hg19: chrX-13615118;