4-8867402-G-GGCCCA

Position:

• chr4-8867402-G-GGCCCA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_018942.3(HMX1):​c.*290_*291insTGGGC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0147 in 1,073,454 control chromosomes in the GnomAD database, including 1,603 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.065 (1065 hom., cov: 33)
  • Exomes 𝑓: 0.0064 (538 hom.)
• Consequence: HMX1 NM_018942.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.999

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 -10 ACMG points.

• BP6: Variant 4-8867402-G-GGCCCA is Benign according to our data. Variant chr4-8867402-G-GGCCCA is described in ClinVar as [Benign]. Clinvar id is 1239047.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMX1	NM_018942.3	c.*290_*291insTGGGC		3_prime_UTR_variant	2/2	ENST00000400677.5	NP_061815.2
HMX1	NM_001306142.2	c.394+3818_394+3819insTGGGC		intron_variant			NP_001293071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMX1	ENST00000400677.5	c.*290_*291insTGGGC		3_prime_UTR_variant	2/2	1	NM_018942.3	ENSP00000383516	P1
HMX1	ENST00000506970.2	c.394+3818_394+3819insTGGGC		intron_variant		1		ENSP00000446997

Frequencies

GnomAD3 genomes AF: 0.0654 AC: 9943 AN: 152132 Hom.: 1062 Cov.: 33

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0224

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0133

Gnomad SAS AF: 0.0401

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.0482

GnomAD4 exome AF: 0.00635 AC: 5852 AN: 921204 Hom.: 538 Cov.: 29 AF XY: 0.00619 AC XY: 2657 AN XY: 429478

Gnomad4 AFR exome AF: 0.230

Gnomad4 AMR exome AF: 0.0153

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00927

Gnomad4 SAS exome AF: 0.0365

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000281

Gnomad4 OTH exome AF: 0.0178

GnomAD4 genome AF: 0.0654 AC: 9963 AN: 152250 Hom.: 1065 Cov.: 33 AF XY: 0.0632 AC XY: 4707 AN XY: 74460

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.0223

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0134

Gnomad4 SAS AF: 0.0394

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000691

Gnomad4 OTH AF: 0.0477

Alfa AF: 0.00810 Hom.: 18

Bravo AF: 0.0729

Asia WGS AF: 0.0360 AC: 124 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 31, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs201818775; hg19: chr4-8869128;