Genetic Variant PHIP:c.*193_*196delTATA (chr6-78940496-TTATA-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_017934.7(PHIP):c.*193_*196delTATA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 130,168 control chromosomes in the GnomAD database, including 14,101 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.46 ( 14044 hom., cov: 0)

Exomes 𝑓: 0.50 ( 57 hom. )

Consequence

PHIP
NM_017934.7 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.562

Variant links:

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 links:

IRAK1BP1 (HGNC:17368): (interleukin 1 receptor associated kinase 1 binding protein 1) Predicted to be involved in I-kappaB kinase/NF-kappaB signaling. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

IRAK1BP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 6-78940496-TTATA-T is Benign according to our data. Variant chr6-78940496-TTATA-T is described in ClinVar as [Benign]. Clinvar id is 1282121.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PHIP	NM_017934.7 link	c.193_196delTATA	3_prime_UTR_variant	Exon 40 of 40	ENST00000275034.5	NP_060404.4	Q8WWQ0
PHIP	XM_005248729.6 link	c.193_196delTATA	3_prime_UTR_variant	Exon 40 of 40		XP_005248786.1	A0A8V8TPV5
PHIP	XM_011535918.4 link	c.193_196delTATA	3_prime_UTR_variant	Exon 37 of 37		XP_011534220.1
IRAK1BP1	XM_047418194.1 link	c.37+4943_37+4946delATAT	intron_variant	Intron 3 of 3		XP_047274150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHIP	ENST00000275034 link	c.193_196delTATA		3_prime_UTR_variant	Exon 40 of 40	1	NM_017934.7	ENSP00000275034.3		Q8WWQ0

Frequencies

GnomAD3 genomes

AF:

0.458

AC:

59253

AN:

129476

Hom.:

14049

Cov.:

show subpopulations

Gnomad AFR

AF:

0.343

Gnomad AMI

AF:

0.502

Gnomad AMR

AF:

0.451

Gnomad ASJ

AF:

0.494

Gnomad EAS

AF:

0.691

Gnomad SAS

AF:

0.639

Gnomad FIN

AF:

0.445

Gnomad MID

AF:

0.464

Gnomad NFE

AF:

0.492

Gnomad OTH

AF:

0.454

GnomAD4 exome

AF:

0.503

AC:

346

AN:

688

Hom.:

AF XY:

0.500

AC XY:

183

AN XY:

366

show subpopulations

Gnomad4 AFR exome

AF:

0.333

AC:

AN:

Gnomad4 AMR exome

AF:

0.611

AC:

AN:

Gnomad4 ASJ exome

AF:

0.500

AC:

AN:

Gnomad4 EAS exome

AF:

0.696

AC:

AN:

Gnomad4 SAS exome

AF:

0.600

AC:

AN:

Gnomad4 FIN exome

AF:

0.443

AC:

AN:

176

Gnomad4 NFE exome

AF:

0.500

AC:

187

AN:

374

Gnomad4 Remaining exome

AF:

0.531

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.457

AC:

59234

AN:

129480

Hom.:

14044

Cov.:

AF XY:

0.461

AC XY:

27978

AN XY:

60750

show subpopulations

Gnomad4 AFR

AF:

0.343

AC:

0.34299

AN:

0.34299

Gnomad4 AMR

AF:

0.451

AC:

0.450736

AN:

0.450736

Gnomad4 ASJ

AF:

0.494

AC:

0.493936

AN:

0.493936

Gnomad4 EAS

AF:

0.692

AC:

0.69175

AN:

0.69175

Gnomad4 SAS

AF:

0.640

AC:

0.63998

AN:

0.63998

Gnomad4 FIN

AF:

0.445

AC:

0.445326

AN:

0.445326

Gnomad4 NFE

AF:

0.492

AC:

0.492091

AN:

0.492091

Gnomad4 OTH

AF:

0.458

AC:

0.457859

AN:

0.457859

Heterozygous variant carriers

1370

2741

4111

5482

6852

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

574

1148

1722

2296

2870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.494

Hom.:

569

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 20, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over