NM_015507.4:c.490C>T

Variant names:

• chrX-13603406-C-T
• rs34613284
• NM_015507.4:c.490C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_015507.4(EGFL6):​c.490C>T​(p.Arg164Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00272 in 1,208,543 control chromosomes in the GnomAD database, including 66 homozygotes. There are 828 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (33 hom., 437 hem., cov: 23)
  • Exomes 𝑓: 0.0015 (33 hom. 391 hem.)
• Consequence: EGFL6 NM_015507.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 7.35
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0047973096).
• BP6: Variant X-13603406-C-T is Benign according to our data. Variant chrX-13603406-C-T is described in ClinVar as Benign. ClinVar VariationId is 712290.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.015 (1680/112229) while in subpopulation AFR AF = 0.052 (1605/30884). AF 95% confidence interval is 0.0499. There are 33 homozygotes in GnomAd4. There are 437 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 33 gene

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.490C>T	p.Arg164Cys	missense	Exon 5 of 12	NP_056322.2
	EGFL6	NM_001167890.2		c.490C>T	p.Arg164Cys	missense	Exon 5 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.490C>T	p.Arg164Cys	missense	Exon 5 of 12	ENSP00000355126.1	Q8IUX8-1
	EGFL6	ENST00000380602.3	TSL:1	c.490C>T	p.Arg164Cys	missense	Exon 5 of 12	ENSP00000369976.3	Q8IUX8-2
	EGFL6	ENST00000857787.1		c.401-2973C>T		intron	N/A	ENSP00000527846.1

Frequencies

GnomAD3 genomes AF: 0.0149 AC: 1676 AN: 112174 Hom.: 33 Cov.: 23

Gnomad AFR AF: 0.0520

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00498

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000376

Gnomad OTH AF: 0.0132

GnomAD2 exomes AF: 0.00432 AC: 778 AN: 179967 AF XY: 0.00277

Gnomad AFR exome AF: 0.0534

Gnomad AMR exome AF: 0.00271

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000495

Gnomad OTH exome AF: 0.00158

GnomAD4 exome AF: 0.00146 AC: 1605 AN: 1096314 Hom.: 33 Cov.: 30 AF XY: 0.00108 AC XY: 391 AN XY: 361780

African (AFR) AF: 0.0506 AC: 1333 AN: 26322

American (AMR) AF: 0.00306 AC: 107 AN: 34915

Ashkenazi Jewish (ASJ) AF: 0.0000517 AC: 1 AN: 19343

East Asian (EAS) AF: 0.00 AC: 0 AN: 30112

South Asian (SAS) AF: 0.0000186 AC: 1 AN: 53678

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40477

Middle Eastern (MID) AF: 0.000969 AC: 4 AN: 4126

European-Non Finnish (NFE) AF: 0.0000309 AC: 26 AN: 841337

Other (OTH) AF: 0.00289 AC: 133 AN: 46004

GnomAD4 genome AF: 0.0150 AC: 1680 AN: 112229 Hom.: 33 Cov.: 23 AF XY: 0.0127 AC XY: 437 AN XY: 34413

African (AFR) AF: 0.0520 AC: 1605 AN: 30884

American (AMR) AF: 0.00498 AC: 53 AN: 10652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2654

East Asian (EAS) AF: 0.00 AC: 0 AN: 3575

South Asian (SAS) AF: 0.00 AC: 0 AN: 2693

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6107

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 215

European-Non Finnish (NFE) AF: 0.0000376 AC: 2 AN: 53226

Other (OTH) AF: 0.0130 AC: 20 AN: 1535

Alfa AF: 0.00260 Hom.: 99

Bravo AF: 0.0168

ESP6500AA AF: 0.0545 AC: 209

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00482 AC: 585

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
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.025	T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.65	T
MetaRNN	Benign	0.0048	T
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		7.4
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.34
Sift	Benign	0.043	D
Sift4G	Uncertain	0.029	D
Polyphen		0.013	B
Vest4		0.17
MVP		0.70
MPC		0.33
ClinPred		0.036	T
GERP RS		5.1
Varity_R		0.22
gMVP		0.74
Mutation Taster		=91/9	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs34613284; hg19: chrX-13621525;