Variant chr16-67169874-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001374675.1(HSF4):c.*89G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00699 in 1,399,744 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0058 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0071 ( 50 hom. )

Consequence

HSF4
NM_001374675.1 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.893

Variant links:

Genes affected

HSF4 (HGNC:5227): (heat shock transcription factor 4) Heat-shock transcription factors (HSFs) activate heat-shock response genes under conditions of heat or other stresses. HSF4 lacks the carboxyl-terminal hydrophobic repeat which is shared among all vertebrate HSFs and has been suggested to be involved in the negative regulation of DNA binding activity. Two alternatively spliced transcripts encoding distinct isoforms and possessing different transcriptional activity have been described. [provided by RefSeq, Jul 2008]

HSF4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

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

BP6

Variant 16-67169874-G-T is Benign according to our data. Variant chr16-67169874-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 320193.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00583 (883/151482) while in subpopulation NFE AF= 0.00793 (539/67968). AF 95% confidence interval is 0.00738. There are 2 homozygotes in gnomad4. There are 467 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 883 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
HSF4	NM_001374675.1 link	c.*89G>T	3_prime_UTR_variant	13/13	ENST00000521374.6	NP_001361604.1
HSF4	NM_001040667.3 link	c.*89G>T	3_prime_UTR_variant	15/15		NP_001035757.1	Q9ULV5-1A0A024R6X7
HSF4	NM_001374674.1 link	c.*89G>T	3_prime_UTR_variant	13/13		NP_001361603.1
HSF4	NM_001538.4 link	c.*89G>T	3_prime_UTR_variant	15/15		NP_001529.2	Q9ULV5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSF4	ENST00000521374.6 link	c.*89G>T		3_prime_UTR_variant	13/13	1	NM_001374675.1	ENSP00000430947.2		Q9ULV5-1

Frequencies

GnomAD3 genomes

AF:

0.00583

AC:

883

AN:

151434

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00158

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.00263

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000833

Gnomad FIN

AF:

0.0215

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00794

Gnomad OTH

AF:

0.00193

GnomAD4 exome

AF:

0.00713

AC:

8902

AN:

1248262

Hom.:

Cov.:

AF XY:

0.00691

AC XY:

4356

AN XY:

630662

show subpopulations

Gnomad4 AFR exome

AF:

0.00145

Gnomad4 AMR exome

AF:

0.00185

Gnomad4 ASJ exome

AF:

0.0000806

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000963

Gnomad4 FIN exome

AF:

0.0196

Gnomad4 NFE exome

AF:

0.00810

Gnomad4 OTH exome

AF:

0.00522

GnomAD4 genome

AF:

0.00583

AC:

883

AN:

151482

Hom.:

Cov.:

AF XY:

0.00632

AC XY:

467

AN XY:

73912

show subpopulations

Gnomad4 AFR

AF:

0.00157

Gnomad4 AMR

AF:

0.00262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0215

Gnomad4 NFE

AF:

0.00793

Gnomad4 OTH

AF:

0.00191

Alfa

AF:

0.00684

Hom.:

Bravo

AF:

0.00443

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cataract 5 multiple types

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.82

Splicing

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