chr1-91319645-G-T

Variant names:

• chr1-91319645-G-T
• rs10493846
• NM_001017975.6:c.2583-255C>A

Variant summary

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

The NM_001017975.6(HFM1):​c.2583-255C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 151,688 control chromosomes in the GnomAD database, including 3,379 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 0.20 (3379 hom., cov: 31)
• Consequence: HFM1 NM_001017975.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.362
• Publications: 4 publications found

Genes affected

HFM1 (HGNC:20193): (helicase for meiosis 1) The protein encoded by this gene is thought to be an ATP-dependent DNA helicase and is expressed mainly in germ-line cells. Defects in this gene are a cause of premature ovarian failure 9 (POF9). [provided by RefSeq, Apr 2014]

HFM1 Gene-Disease associations (from GenCC):

• premature ovarian failure 9

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: NO_KNOWN Submitted by: King Faisal Specialist Hospital and Research Center

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HFM1	NM_001017975.6	c.2583-255C>A		intron_variant	Intron 23 of 38	ENST00000370425.8	NP_001017975.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HFM1	ENST00000370425.8	c.2583-255C>A		intron_variant	Intron 23 of 38	1	NM_001017975.6	ENSP00000359454.3
HFM1	ENST00000430465.1	c.348-255C>A		intron_variant	Intron 5 of 18	1		ENSP00000387661.1
HFM1	ENST00000462405.5	n.509-255C>A		intron_variant	Intron 6 of 20	2
HFM1	ENST00000497520.1	n.241-255C>A		intron_variant	Intron 3 of 4	3

Frequencies

GnomAD3 genomes AF: 0.198 AC: 29947 AN: 151570 Hom.: 3379 Cov.: 31

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.00386

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.197 AC: 29940 AN: 151688 Hom.: 3379 Cov.: 31 AF XY: 0.191 AC XY: 14115 AN XY: 74084

African (AFR) AF: 0.136 AC: 5632 AN: 41346

American (AMR) AF: 0.175 AC: 2671 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 463 AN: 3468

East Asian (EAS) AF: 0.00368 AC: 19 AN: 5170

South Asian (SAS) AF: 0.123 AC: 590 AN: 4800

European-Finnish (FIN) AF: 0.197 AC: 2068 AN: 10484

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17809 AN: 67876

Other (OTH) AF: 0.199 AC: 418 AN: 2104

Alfa AF: 0.196 Hom.: 1345

Bravo AF: 0.192

Asia WGS AF: 0.0610 AC: 211 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.5
DANN	Benign	0.24
PhyloP100		0.36
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: rs10493846; hg19: chr1-91785202;