chr6-78990442-A-G

Variant names:

• chr6-78990442-A-G
• rs1415863
• NM_017934.7:c.2319+426T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017934.7(PHIP):​c.2319+426T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.926 in 152,178 control chromosomes in the GnomAD database, including 65,305 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 0.93 (65305 hom., cov: 31)
• Consequence: PHIP NM_017934.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.319
• Publications: 3 publications found

Genes affected

PHIP (HGNC:15673): (pleckstrin homology domain interacting protein) This gene encodes a protein that binds to the insulin receptor substrate 1 protein and regulates glucose transporter translocation in skeletal muscle cells. The encoded protein may also regulate growth and survival of pancreatic beta cells. Elevated copy number of this gene may be associated with melanoma severity and the encoded protein may promote melanoma metastasis in human patients. [provided by RefSeq, Oct 2016]

PHIP Gene-Disease associations (from GenCC):

• developmental delay, intellectual disability, obesity, and dysmorphic features

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
• PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHIP	NM_017934.7	c.2319+426T>C		intron_variant	Intron 20 of 39	ENST00000275034.5	NP_060404.4
PHIP	XM_005248729.6	c.2316+426T>C		intron_variant	Intron 20 of 39		XP_005248786.1
PHIP	XM_011535918.4	c.1803+426T>C		intron_variant	Intron 17 of 36		XP_011534220.1
PHIP	XM_011535919.2	c.2319+426T>C		intron_variant	Intron 20 of 25		XP_011534221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHIP	ENST00000275034.5	c.2319+426T>C		intron_variant	Intron 20 of 39	1	NM_017934.7	ENSP00000275034.3

Frequencies

GnomAD3 genomes AF: 0.926 AC: 140776 AN: 152060 Hom.: 65266 Cov.: 31

Gnomad AFR AF: 0.872

Gnomad AMI AF: 0.976

Gnomad AMR AF: 0.904

Gnomad ASJ AF: 0.950

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.945

Gnomad FIN AF: 0.934

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.953

Gnomad OTH AF: 0.933

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

GnomAD4 genome AF: 0.926 AC: 140876 AN: 152178 Hom.: 65305 Cov.: 31 AF XY: 0.925 AC XY: 68827 AN XY: 74394

African (AFR) AF: 0.872 AC: 36220 AN: 41524

American (AMR) AF: 0.904 AC: 13815 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.950 AC: 3298 AN: 3470

East Asian (EAS) AF: 0.995 AC: 5146 AN: 5170

South Asian (SAS) AF: 0.945 AC: 4557 AN: 4822

European-Finnish (FIN) AF: 0.934 AC: 9893 AN: 10594

Middle Eastern (MID) AF: 0.973 AC: 286 AN: 294

European-Non Finnish (NFE) AF: 0.953 AC: 64800 AN: 67992

Other (OTH) AF: 0.933 AC: 1971 AN: 2112

Alfa AF: 0.942 Hom.: 34633

Bravo AF: 0.921

Asia WGS AF: 0.960 AC: 3331 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.0
DANN	Benign	0.51
PhyloP100		-0.32
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: rs1415863; hg19: chr6-79700159;