rs755109

Variant names:

• chr9-97933921-T-C
• rs755109
• NM_197978.3:c.173+2250A>G

Variant summary

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

The NM_197978.3(HEMGN):​c.173+2250A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,108 control chromosomes in the GnomAD database, including 7,700 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 0.30 (7700 hom., cov: 32)
• Consequence: HEMGN NM_197978.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172
• Publications: 25 publications found

Genes affected

HEMGN (HGNC:17509): (hemogen) Predicted to be involved in regulation of osteoblast differentiation. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEMGN	NM_197978.3	c.173+2250A>G		intron_variant	Intron 2 of 3	ENST00000616898.2	NP_932095.1
HEMGN	NM_018437.5	c.173+2250A>G		intron_variant	Intron 3 of 4		NP_060907.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEMGN	ENST00000616898.2	c.173+2250A>G		intron_variant	Intron 2 of 3	1	NM_197978.3	ENSP00000480020.1
HEMGN	ENST00000259456.7	c.173+2250A>G		intron_variant	Intron 3 of 4	1		ENSP00000259456.2

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45762 AN: 151990 Hom.: 7694 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.301 AC: 45799 AN: 152108 Hom.: 7700 Cov.: 32 AF XY: 0.301 AC XY: 22374 AN XY: 74360

African (AFR) AF: 0.179 AC: 7425 AN: 41520

American (AMR) AF: 0.327 AC: 4991 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1363 AN: 3468

East Asian (EAS) AF: 0.140 AC: 725 AN: 5174

South Asian (SAS) AF: 0.205 AC: 990 AN: 4830

European-Finnish (FIN) AF: 0.406 AC: 4285 AN: 10560

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.367 AC: 24966 AN: 67958

Other (OTH) AF: 0.348 AC: 736 AN: 2112

Alfa AF: 0.338 Hom.: 27968

Bravo AF: 0.291

Asia WGS AF: 0.237 AC: 823 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.6
DANN	Benign	0.54
PhyloP100		-0.17
Mutation Taster		=99/1	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: rs755109; hg19: chr9-100696203;