Variant 16-67165456-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001374675.1(HSF4):c.124-66C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00784 in 1,409,102 control chromosomes in the GnomAD database, including 593 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 339 hom., cov: 32)

Exomes 𝑓: 0.0044 ( 254 hom. )

Consequence

HSF4
NM_001374675.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.882

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=-0.79).

BP6

Variant 16-67165456-C-G is Benign according to our data. Variant chr16-67165456-C-G is described in ClinVar as [Benign]. Clinvar id is 1271790.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
HSF4	NM_001374675.1 linkuse as main transcript	c.124-66C>G	intron_variant	ENST00000521374.6
HSF4	NM_001040667.3 linkuse as main transcript	c.124-66C>G	intron_variant
HSF4	NM_001374674.1 linkuse as main transcript	c.124-66C>G	intron_variant
HSF4	NM_001538.4 linkuse as main transcript	c.124-66C>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSF4	ENST00000521374.6 linkuse as main transcript	c.124-66C>G		intron_variant		1	NM_001374675.1	P4	Q9ULV5-1

Frequencies

GnomAD3 genomes

AF:

0.0363

AC:

5515

AN:

152114

Hom.:

337

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0178

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.0258

GnomAD4 exome

AF:

0.00439

AC:

5516

AN:

1256870

Hom.:

254

Cov.:

AF XY:

0.00391

AC XY:

2485

AN XY:

635262

show subpopulations

Gnomad4 AFR exome

AF:

0.134

Gnomad4 AMR exome

AF:

0.00909

Gnomad4 ASJ exome

AF:

0.00331

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000292

Gnomad4 FIN exome

AF:

0.0000194

Gnomad4 NFE exome

AF:

0.000569

Gnomad4 OTH exome

AF:

0.00960

GnomAD4 genome

AF:

0.0364

AC:

5537

AN:

152232

Hom.:

339

Cov.:

AF XY:

0.0352

AC XY:

2617

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.124

Gnomad4 AMR

AF:

0.0178

Gnomad4 ASJ

AF:

0.00374

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000838

Gnomad4 OTH

AF:

0.0250

Alfa

AF:

0.0298

Hom.:

Bravo

AF:

0.0415

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 02, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.4

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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