rs6633092

Variant names:

• chrX-13600045-G-A
• rs6633092
• NM_015507.4:c.351G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_015507.4(EGFL6):​c.351G>A​(p.Lys117Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00477 in 1,209,514 control chromosomes in the GnomAD database, including 131 homozygotes. There are 1,574 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (65 hom., 689 hem., cov: 22)
  • Exomes 𝑓: 0.0030 (66 hom. 885 hem.)
• Consequence: EGFL6 NM_015507.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.82
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant X-13600045-G-A is Benign according to our data. Variant chrX-13600045-G-A is described in ClinVar as Benign. ClinVar VariationId is 780682.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.82 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0734 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015507.4. 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
	EGFL6	NM_015507.4	MANE Select	c.351G>A	p.Lys117Lys	synonymous	Exon 4 of 12	NP_056322.2
	EGFL6	NM_001167890.2		c.351G>A	p.Lys117Lys	synonymous	Exon 4 of 12	NP_001161362.1	Q8IUX8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFL6	ENST00000361306.6	TSL:1 MANE Select	c.351G>A	p.Lys117Lys	synonymous	Exon 4 of 12	ENSP00000355126.1	Q8IUX8-1
	EGFL6	ENST00000380602.3	TSL:1	c.351G>A	p.Lys117Lys	synonymous	Exon 4 of 12	ENSP00000369976.3	Q8IUX8-2
	EGFL6	ENST00000857787.1		c.351G>A	p.Lys117Lys	synonymous	Exon 4 of 11	ENSP00000527846.1

Frequencies

GnomAD3 genomes AF: 0.0223 AC: 2493 AN: 111724 Hom.: 64 Cov.: 22

Gnomad AFR AF: 0.0756

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0100

Gnomad ASJ AF: 0.000377

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000371

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0169

Gnomad NFE AF: 0.000696

Gnomad OTH AF: 0.0180

GnomAD2 exomes AF: 0.00735 AC: 1344 AN: 182950 AF XY: 0.00466

Gnomad AFR exome AF: 0.0796

Gnomad AMR exome AF: 0.00762

Gnomad ASJ exome AF: 0.00107

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000627

Gnomad NFE exome AF: 0.000831

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00297 AC: 3257 AN: 1097739 Hom.: 66 Cov.: 30 AF XY: 0.00244 AC XY: 885 AN XY: 363155

African (AFR) AF: 0.0776 AC: 2045 AN: 26341

American (AMR) AF: 0.00836 AC: 294 AN: 35187

Ashkenazi Jewish (ASJ) AF: 0.00103 AC: 20 AN: 19372

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30197

South Asian (SAS) AF: 0.000333 AC: 18 AN: 54126

European-Finnish (FIN) AF: 0.0000494 AC: 2 AN: 40498

Middle Eastern (MID) AF: 0.00701 AC: 29 AN: 4137

European-Non Finnish (NFE) AF: 0.000627 AC: 528 AN: 841812

Other (OTH) AF: 0.00695 AC: 320 AN: 46069

GnomAD4 genome AF: 0.0224 AC: 2509 AN: 111775 Hom.: 65 Cov.: 22 AF XY: 0.0203 AC XY: 689 AN XY: 33947

African (AFR) AF: 0.0759 AC: 2334 AN: 30740

American (AMR) AF: 0.00990 AC: 104 AN: 10509

Ashkenazi Jewish (ASJ) AF: 0.000377 AC: 1 AN: 2652

East Asian (EAS) AF: 0.00 AC: 0 AN: 3553

South Asian (SAS) AF: 0.000744 AC: 2 AN: 2689

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6034

Middle Eastern (MID) AF: 0.0185 AC: 4 AN: 216

European-Non Finnish (NFE) AF: 0.000696 AC: 37 AN: 53180

Other (OTH) AF: 0.0178 AC: 27 AN: 1517

Alfa AF: 0.0129 Hom.: 80

Bravo AF: 0.0265

EpiCase AF: 0.00115

EpiControl AF: 0.00131

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	6.5
DANN	Benign	0.75
PhyloP100		1.8
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: rs6633092; hg19: chrX-13618164;