chr6-122425793-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004506.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSF2	NM_004506.4	MANE Select	c.1176+2107G>T		intron	N/A	NP_004497.1	Q03933-1
	HSF2	NM_001135564.1		c.1176+2107G>T		intron	N/A	NP_001129036.1	Q03933-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSF2	ENST00000368455.9	TSL:1 MANE Select	c.1176+2107G>T		intron	N/A	ENSP00000357440.4	Q03933-1
	HSF2	ENST00000452194.5	TSL:1	c.1176+2107G>T		intron	N/A	ENSP00000400380.1	Q03933-2
	HSF2	ENST00000924428.1		c.1176+2107G>T		intron	N/A	ENSP00000594487.1

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

African (AFR) AF: 0.512 AC: 21204 AN: 41414

American (AMR) AF: 0.619 AC: 9423 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2008 AN: 3464

East Asian (EAS) AF: 0.461 AC: 2374 AN: 5154

South Asian (SAS) AF: 0.679 AC: 3264 AN: 4808

European-Finnish (FIN) AF: 0.543 AC: 5723 AN: 10540

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36943 AN: 67858

Other (OTH) AF: 0.542 AC: 1141 AN: 2106

Alfa AF: 0.401 Hom.: 1081

Bravo AF: 0.544

Asia WGS AF: 0.568 AC: 1970 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.1
DANN	Benign	0.78
PhyloP100		0.12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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