4-8867531-A-G

Position:

• chr4-8867531-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018942.3(HMX1):​c.*162T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.905 in 1,184,762 control chromosomes in the GnomAD database, including 486,023 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.91 (63091 hom., cov: 30)
  • Exomes 𝑓: 0.90 (422932 hom.)
• Consequence: HMX1 NM_018942.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.414

Genes affected

HMX1 (HGNC:5017): (H6 family homeobox 1) This gene encodes a transcription factor that belongs to the H6 family of homeobox proteins. This protein can bind a 5'-CAAG-3' core DNA sequence, and it is involved in the development of craniofacial structures. Mutations in this gene cause oculoauricular syndrome, a disorder of the eye and external ear. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 4-8867531-A-G is Benign according to our data. Variant chr4-8867531-A-G is described in ClinVar as [Benign]. Clinvar id is 1286769.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMX1	NM_018942.3	c.*162T>C		3_prime_UTR_variant	2/2	ENST00000400677.5	NP_061815.2
HMX1	NM_001306142.2	c.394+3690T>C		intron_variant			NP_001293071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMX1	ENST00000400677.5	c.*162T>C		3_prime_UTR_variant	2/2	1	NM_018942.3	ENSP00000383516	P1
HMX1	ENST00000506970.2	c.394+3690T>C		intron_variant		1		ENSP00000446997

Frequencies

GnomAD3 genomes AF: 0.910 AC: 138241 AN: 151922 Hom.: 63027 Cov.: 30

Gnomad AFR AF: 0.931

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.927

Gnomad ASJ AF: 0.833

Gnomad EAS AF: 0.922

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.915

Gnomad MID AF: 0.860

Gnomad NFE AF: 0.907

Gnomad OTH AF: 0.895

GnomAD4 exome AF: 0.905 AC: 934177 AN: 1032722 Hom.: 422932 Cov.: 46 AF XY: 0.904 AC XY: 440321 AN XY: 487342

Gnomad4 AFR exome AF: 0.929

Gnomad4 AMR exome AF: 0.935

Gnomad4 ASJ exome AF: 0.834

Gnomad4 EAS exome AF: 0.942

Gnomad4 SAS exome AF: 0.755

Gnomad4 FIN exome AF: 0.897

Gnomad4 NFE exome AF: 0.908

Gnomad4 OTH exome AF: 0.890

GnomAD4 genome AF: 0.910 AC: 138366 AN: 152040 Hom.: 63091 Cov.: 30 AF XY: 0.908 AC XY: 67486 AN XY: 74326

Gnomad4 AFR AF: 0.931

Gnomad4 AMR AF: 0.928

Gnomad4 ASJ AF: 0.833

Gnomad4 EAS AF: 0.922

Gnomad4 SAS AF: 0.749

Gnomad4 FIN AF: 0.915

Gnomad4 NFE AF: 0.907

Gnomad4 OTH AF: 0.896

Alfa AF: 0.911 Hom.: 7836

Bravo AF: 0.916

Asia WGS AF: 0.881 AC: 3061 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.7
DANN	Benign	0.54

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: rs13303067; hg19: chr4-8869257;