8-144476070-A-G

Variant names:

• chr8-144476070-A-G
• rs750472
• NM_003923.3:c.-314T>C

Variant summary

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

The NM_003923.3(FOXH1):​c.-314T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FOXH1 NM_003923.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.68
• Publications: 28 publications found

Genes affected

FOXH1 (HGNC:3814): (forkhead box H1) FOXH1 encodes a human homolog of Xenopus forkhead activin signal transducer-1. FOXH1 protein binds SMAD2 and activates an activin response element via binding the DNA motif TGT(G/T)(T/G)ATT. [provided by RefSeq, Jul 2008]

FOXH1 Gene-Disease associations (from GenCC):

• congenital heart malformation

  Inheritance: Unknown Classification: LIMITED Submitted by: Laboratory for Molecular Medicine

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=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003923.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXH1	NM_003923.3	MANE Select	c.-314T>C		upstream_gene	N/A	NP_003914.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXH1	ENST00000377317.5	TSL:1 MANE Select	c.-314T>C		upstream_gene	N/A	ENSP00000366534.4
	FOXH1	ENST00000525197.1	TSL:3	n.-247T>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 162966 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 82036

African (AFR) AF: 0.00 AC: 0 AN: 5244

American (AMR) AF: 0.00 AC: 0 AN: 4636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6564

East Asian (EAS) AF: 0.00 AC: 0 AN: 14854

South Asian (SAS) AF: 0.00 AC: 0 AN: 1548

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13548

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 906

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 104526

Other (OTH) AF: 0.00 AC: 0 AN: 11140

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.25
DANN	Benign	0.30
PhyloP100		-2.7
PromoterAI		0.015	Neutral

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: rs750472; hg19: chr8-145701453;