6-122425793-G-T

Variant names:

• chr6-122425793-G-T
• rs576247
• NM_004506.4:c.1176+2107G>T

Variant summary

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

The NM_004506.4(HSF2):​c.1176+2107G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 151,774 control chromosomes in the GnomAD database, including 22,803 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 0.55 (22803 hom., cov: 32)
• Consequence: HSF2 NM_004506.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117

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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSF2	NM_004506.4	c.1176+2107G>T		intron_variant	Intron 10 of 12	ENST00000368455.9	NP_004497.1
HSF2	NM_001135564.1	c.1176+2107G>T		intron_variant	Intron 10 of 11		NP_001129036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSF2	ENST00000368455.9	c.1176+2107G>T		intron_variant	Intron 10 of 12	1	NM_004506.4	ENSP00000357440.4
HSF2	ENST00000452194.5	c.1176+2107G>T		intron_variant	Intron 10 of 11	1		ENSP00000400380.1
HSF2	ENST00000465214.2	c.489+2107G>T		intron_variant	Intron 3 of 4	2		ENSP00000477405.1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82741 AN: 151656 Hom.: 22807 Cov.: 32

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.550

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.545 AC: 82763 AN: 151774 Hom.: 22803 Cov.: 32 AF XY: 0.549 AC XY: 40716 AN XY: 74190

Gnomad4 AFR AF: 0.512

Gnomad4 AMR AF: 0.619

Gnomad4 ASJ AF: 0.580

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.679

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.542

Alfa AF: 0.391 Hom.: 969

Bravo AF: 0.544

Asia WGS AF: 0.568 AC: 1970 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.1
DANN	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs576247; hg19: chr6-122746938; COSMIC: COSV63773639;