6-78940496-TTATATATATATA-TTATATA

Variant names:

• chr6-78940496-TTATATA-T
• rs55984056
• NM_017934.7:c.*191_*196delTATATA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_017934.7(PHIP):​c.*191_*196delTATATA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 130,786 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000061 (0 hom., cov: 0)
  • Exomes 𝑓: 0.013 (0 hom.)
• Consequence: PHIP NM_017934.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.562

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]

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0128 (9/702) while in subpopulation NFE AF= 0.0206 (8/388). AF 95% confidence interval is 0.0103. There are 0 homozygotes in gnomad4_exome. There are 4 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHIP	NM_017934.7	c.*191_*196delTATATA		3_prime_UTR_variant	Exon 40 of 40	ENST00000275034.5	NP_060404.4
PHIP	XM_005248729.6	c.*191_*196delTATATA		3_prime_UTR_variant	Exon 40 of 40		XP_005248786.1
PHIP	XM_011535918.4	c.*191_*196delTATATA		3_prime_UTR_variant	Exon 37 of 37		XP_011534220.1
IRAK1BP1	XM_047418194.1	c.*37+4941_*37+4946delATATAT		intron_variant	Intron 3 of 3		XP_047274150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHIP	ENST00000275034	c.*191_*196delTATATA		3_prime_UTR_variant	Exon 40 of 40	1	NM_017934.7	ENSP00000275034.3

Frequencies

GnomAD3 genomes AF: 0.0000615 AC: 8 AN: 130084 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000570

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000861

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000245

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000624

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0128 AC: 9 AN: 702 Hom.: 0 AF XY: 0.0106 AC XY: 4 AN XY: 376

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00568

Gnomad4 NFE exome AF: 0.0206

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000615 AC: 8 AN: 130084 Hom.: 0 Cov.: 0 AF XY: 0.0000819 AC XY: 5 AN XY: 61026

Gnomad4 AFR AF: 0.0000570

Gnomad4 AMR AF: 0.0000861

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000245

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000624

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs55984056; hg19: chr6-79650213;