16-67165456-C-G

Position:

• chr16-67165456-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.882

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSF4	NM_001374675.1	c.124-66C>G		intron_variant		ENST00000521374.6
HSF4	NM_001040667.3	c.124-66C>G		intron_variant
HSF4	NM_001374674.1	c.124-66C>G		intron_variant
HSF4	NM_001538.4	c.124-66C>G		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0363 AC: 5515 AN: 152114 Hom.: 337 Cov.: 32

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.: 19 AF XY: 0.00391 AC XY: 2485 AN XY: 635262

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.: 32 AF XY: 0.0352 AC XY: 2617 AN XY: 74444

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.: 29

Bravo AF: 0.0415

Asia WGS AF: 0.0110 AC: 37 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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

Other links and lift over

dbSNP: rs115471631; hg19: chr16-67199359;