chr11-94054592-A-G

Variant names:

• chr11-94054592-A-G
• rs7127348
• NM_001098672.2:c.415+8675A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098672.2(HEPHL1):​c.415+8675A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 152,060 control chromosomes in the GnomAD database, including 19,944 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 0.50 (19944 hom., cov: 32)
• Consequence: HEPHL1 NM_001098672.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.540
• Publications: 6 publications found

Genes affected

HEPHL1 (HGNC:30477): (hephaestin like 1) Enables ferroxidase activity. Involved in cellular iron ion homeostasis. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

PHB1P16 (HGNC:51549): (PHB1 pseudogene 16)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEPHL1	NM_001098672.2	c.415+8675A>G		intron_variant	Intron 2 of 19	ENST00000315765.10	NP_001092142.1
PHB1P16		n.94054592A>G		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEPHL1	ENST00000315765.10	c.415+8675A>G		intron_variant	Intron 2 of 19	5	NM_001098672.2	ENSP00000313699.9

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76271 AN: 151942 Hom.: 19946 Cov.: 32

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.502

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

GnomAD4 genome AF: 0.502 AC: 76303 AN: 152060 Hom.: 19944 Cov.: 32 AF XY: 0.504 AC XY: 37493 AN XY: 74334

African (AFR) AF: 0.358 AC: 14849 AN: 41484

American (AMR) AF: 0.492 AC: 7508 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2065 AN: 3472

East Asian (EAS) AF: 0.421 AC: 2170 AN: 5158

South Asian (SAS) AF: 0.589 AC: 2836 AN: 4816

European-Finnish (FIN) AF: 0.559 AC: 5914 AN: 10572

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.575 AC: 39098 AN: 67968

Other (OTH) AF: 0.498 AC: 1051 AN: 2112

Alfa AF: 0.548 Hom.: 99879

Bravo AF: 0.486

Asia WGS AF: 0.471 AC: 1638 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	6.4
DANN	Benign	0.48
PhyloP100		-0.54
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: rs7127348; hg19: chr11-93787758;