chrX-13600042-C-T

Variant names:

• chrX-13600042-C-T
• rs16999038
• NM_015507.4:c.348C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_015507.4(EGFL6):​c.348C>T​(p.Tyr116Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00215 in 1,209,547 control chromosomes in the GnomAD database, including 33 homozygotes. There are 703 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (19 hom., 335 hem., cov: 22)
  • Exomes 𝑓: 0.0012 (14 hom. 368 hem.)
• Consequence: EGFL6 NM_015507.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.64

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=-0.39).
• BP6: Variant X-13600042-C-T is Benign according to our data. Variant chrX-13600042-C-T is described in ClinVar as [Benign]. Clinvar id is 777786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.64 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0111 (1242/111849) while in subpopulation AFR AF = 0.038 (1170/30801). AF 95% confidence interval is 0.0362. There are 19 homozygotes in GnomAd4. There are 335 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 19 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFL6	NM_015507.4	c.348C>T	p.Tyr116Tyr	synonymous_variant	Exon 4 of 12	ENST00000361306.6	NP_056322.2
EGFL6	NM_001167890.2	c.348C>T	p.Tyr116Tyr	synonymous_variant	Exon 4 of 12		NP_001161362.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFL6	ENST00000361306.6	c.348C>T	p.Tyr116Tyr	synonymous_variant	Exon 4 of 12	1	NM_015507.4	ENSP00000355126.1
EGFL6	ENST00000380602.3	c.348C>T	p.Tyr116Tyr	synonymous_variant	Exon 4 of 12	1		ENSP00000369976.3

Frequencies

GnomAD3 genomes AF: 0.0111 AC: 1243 AN: 111796 Hom.: 19 Cov.: 22

Gnomad AFR AF: 0.0381

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00476

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: 0.000113

Gnomad OTH AF: 0.0107

GnomAD2 exomes AF: 0.00320 AC: 586 AN: 183013 AF XY: 0.00212

Gnomad AFR exome AF: 0.0405

Gnomad AMR exome AF: 0.00135

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000110

Gnomad OTH exome AF: 0.00155

GnomAD4 exome AF: 0.00124 AC: 1356 AN: 1097698 Hom.: 14 Cov.: 30 AF XY: 0.00101 AC XY: 368 AN XY: 363056

Gnomad4 AFR exome AF: 0.0432 AC: 1138 AN: 26373

Gnomad4 AMR exome AF: 0.00188 AC: 66 AN: 35199

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 19376

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 30193

Gnomad4 SAS exome AF: 0.000129 AC: 7 AN: 54117

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 40511

Gnomad4 NFE exome AF: 0.0000297 AC: 25 AN: 841715

Gnomad4 Remaining exome AF: 0.00252 AC: 116 AN: 46078

GnomAD4 genome AF: 0.0111 AC: 1242 AN: 111849 Hom.: 19 Cov.: 22 AF XY: 0.00984 AC XY: 335 AN XY: 34031

Gnomad4 AFR AF: 0.0380 AC: 0.0379858 AN: 0.0379858

Gnomad4 AMR AF: 0.00475 AC: 0.00475014 AN: 0.00475014

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000113 AC: 0.000112837 AN: 0.000112837

Gnomad4 OTH AF: 0.0105 AC: 0.0105263 AN: 0.0105263

Alfa AF: 0.00497 Hom.: 31

Bravo AF: 0.0133

EpiCase AF: 0.00

EpiControl AF: 0.0000594

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 25, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	6.7
DANN	Benign	0.79
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

Publications

LitVar

Other links and lift over

dbSNP: rs16999038; hg19: chrX-13618161;