rs549302

Positions:

• chr6-122413827-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004506.4(HSF2):​c.455+178G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 151,784 control chromosomes in the GnomAD database, including 22,432 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (22432 hom., cov: 31)
• Consequence: HSF2 NM_004506.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810

Genes affected

HSF2 (HGNC:5225): (heat shock transcription factor 2) The protein encoded by this gene belongs to the HSF family of transcription factors that bind specifically to the heat-shock promoter element and activate transcription. Heat shock transcription factors activate heat-shock response genes under conditions of heat or other stresses. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSF2	NM_004506.4	c.455+178G>A		intron_variant		ENST00000368455.9	NP_004497.1
HSF2	NM_001135564.1	c.455+178G>A		intron_variant			NP_001129036.1
HSF2	NM_001243094.2	c.455+178G>A		intron_variant			NP_001230023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSF2	ENST00000368455.9	c.455+178G>A		intron_variant		1	NM_004506.4	ENSP00000357440	P1
HSF2	ENST00000452194.5	c.455+178G>A		intron_variant		1		ENSP00000400380

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82013 AN: 151666 Hom.: 22435 Cov.: 31

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.679

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.538

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.540 AC: 82035 AN: 151784 Hom.: 22432 Cov.: 31 AF XY: 0.544 AC XY: 40335 AN XY: 74150

Gnomad4 AFR AF: 0.496

Gnomad4 AMR AF: 0.616

Gnomad4 ASJ AF: 0.580

Gnomad4 EAS AF: 0.460

Gnomad4 SAS AF: 0.677

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.538

Alfa AF: 0.538 Hom.: 2736

Bravo AF: 0.539

Asia WGS AF: 0.568 AC: 1974 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.8
DANN	Benign	0.52

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

Other links and lift over

dbSNP: rs549302; hg19: chr6-122734972; COSMIC: COSV63773613;