rs556439

Variant names:

• chr6-122423864-A-G
• rs556439
• NM_004506.4:c.1176+178A>G

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+178A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 151,970 control chromosomes in the GnomAD database, including 37,588 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 0.70 (37588 hom., cov: 32)
• Consequence: HSF2 NM_004506.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.801
• Publications: 13 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSF2	NM_004506.4	c.1176+178A>G		intron_variant	Intron 10 of 12	ENST00000368455.9	NP_004497.1
HSF2	NM_001135564.1	c.1176+178A>G		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+178A>G		intron_variant	Intron 10 of 12	1	NM_004506.4	ENSP00000357440.4
HSF2	ENST00000452194.5	c.1176+178A>G		intron_variant	Intron 10 of 11	1		ENSP00000400380.1
HSF2	ENST00000465214.2	c.489+178A>G		intron_variant	Intron 3 of 4	2		ENSP00000477405.1

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106620 AN: 151852 Hom.: 37556 Cov.: 32

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.697

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

GnomAD4 genome AF: 0.702 AC: 106706 AN: 151970 Hom.: 37588 Cov.: 32 AF XY: 0.701 AC XY: 52025 AN XY: 74264

African (AFR) AF: 0.686 AC: 28422 AN: 41458

American (AMR) AF: 0.740 AC: 11284 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.748 AC: 2595 AN: 3468

East Asian (EAS) AF: 0.716 AC: 3707 AN: 5178

South Asian (SAS) AF: 0.774 AC: 3726 AN: 4812

European-Finnish (FIN) AF: 0.652 AC: 6889 AN: 10568

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.702 AC: 47717 AN: 67926

Other (OTH) AF: 0.700 AC: 1475 AN: 2108

Alfa AF: 0.707 Hom.: 116701

Bravo AF: 0.706

Asia WGS AF: 0.744 AC: 2590 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.55
DANN	Benign	0.75
PhyloP100		-0.80
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: rs556439; hg19: chr6-122745009; COSMIC: COSV63773632;