Genetic Variant FHIP1A:p.Ser4Ser (chr4-151566271-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001109977.3(FHIP1A):c.12G>A(p.Ser4Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000645 in 1,548,470 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0031 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00038 ( 4 hom. )

Consequence

FHIP1A
NM_001109977.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.16

Variant links:

Genes affected

FHIP1A (HGNC:34237): (FHF complex subunit HOOK interacting protein 1A) Involved in protein localization to perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

FHIP1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 4-151566271-G-A is Benign according to our data. Variant chr4-151566271-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2655125.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.16 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FHIP1A	NM_001109977.3 link	c.12G>A	p.Ser4Ser	synonymous_variant	Exon 4 of 14	ENST00000435205.6	NP_001103447.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FHIP1A	ENST00000435205.6 link	c.12G>A	p.Ser4Ser	synonymous_variant	Exon 4 of 14	5	NM_001109977.3	ENSP00000413196.1		Q05DH4

Frequencies

GnomAD3 genomes

AF:

0.00307

AC:

467

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00973

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00336

GnomAD3 exomes

AF:

0.000814

AC:

127

AN:

156010

Hom.:

AF XY:

0.000593

AC XY:

AN XY:

82598

show subpopulations

Gnomad AFR exome

AF:

0.00981

Gnomad AMR exome

AF:

0.000981

Gnomad ASJ exome

AF:

0.000236

Gnomad EAS exome

AF:

0.000184

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000595

Gnomad NFE exome

AF:

0.000282

Gnomad OTH exome

AF:

0.000687

GnomAD4 exome

AF:

0.000381

AC:

532

AN:

1396250

Hom.:

Cov.:

AF XY:

0.000321

AC XY:

221

AN XY:

688794

show subpopulations

Gnomad4 AFR exome

AF:

0.00966

Gnomad4 AMR exome

AF:

0.00143

Gnomad4 ASJ exome

AF:

0.000119

Gnomad4 EAS exome

AF:

0.0000560

Gnomad4 SAS exome

AF:

0.0000253

Gnomad4 FIN exome

AF:

0.000142

Gnomad4 NFE exome

AF:

0.000112

Gnomad4 OTH exome

AF:

0.000708

GnomAD4 genome

AF:

0.00307

AC:

467

AN:

152220

Hom.:

Cov.:

AF XY:

0.00269

AC XY:

200

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.00970

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00111

Hom.:

Bravo

AF:

0.00382

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FHIP1A: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

2.3

DANN

Benign

0.65

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