rs11642409

Variant names:

• chr16-67169874-G-A
• rs11642409
• ENST00000434833.6:n.*516G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-67169874-G-A
• chr16-67169874-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000434833.6(HSF4):​n.*516G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000032 in 1,248,340 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000032 (0 hom.)
• Consequence: HSF4 ENST00000434833.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.893
• Publications: 0 publications found

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]

HSF4 Gene-Disease associations (from GenCC):

• cataract 5 multiple types

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• early-onset lamellar cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• total early-onset cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSF4	NM_001374675.1	c.*89G>A		3_prime_UTR_variant	Exon 13 of 13	ENST00000521374.6	NP_001361604.1
HSF4	NM_001040667.3	c.*89G>A		3_prime_UTR_variant	Exon 15 of 15		NP_001035757.1
HSF4	NM_001374674.1	c.*89G>A		3_prime_UTR_variant	Exon 13 of 13		NP_001361603.1
HSF4	NM_001538.4	c.*89G>A		3_prime_UTR_variant	Exon 15 of 15		NP_001529.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSF4	ENST00000521374.6	c.*89G>A		3_prime_UTR_variant	Exon 13 of 13	1	NM_001374675.1	ENSP00000430947.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000320 AC: 4 AN: 1248340 Hom.: 0 Cov.: 19 AF XY: 0.00000476 AC XY: 3 AN XY: 630690

African (AFR) AF: 0.00 AC: 0 AN: 29584

American (AMR) AF: 0.00 AC: 0 AN: 44208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24810

East Asian (EAS) AF: 0.00 AC: 0 AN: 38788

South Asian (SAS) AF: 0.0000366 AC: 3 AN: 82032

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5224

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 922230

Other (OTH) AF: 0.0000187 AC: 1 AN: 53430

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Benign	0.88
PhyloP100		0.89
PromoterAI		0.14	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11642409; hg19: chr16-67203777;