rs228918

Variant names:

• chr22-37110640-T-C
• rs228918
• XM_024452167.2:c.-187A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_024452167.2(TMPRSS6):​c.-187A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 151,866 control chromosomes in the GnomAD database, including 12,623 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 0.41 (12623 hom., cov: 31)
• Consequence: TMPRSS6 XM_024452167.2 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.361

Genes affected

TMPRSS6 (HGNC:16517): (transmembrane serine protease 6) The protein encoded by this gene is a type II transmembrane serine proteinase that is found attached to the cell surface. The encoded protein may be involved in matrix remodeling processes in the liver. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS6	XM_024452167.2	c.-187A>G		upstream_gene_variant			XP_024307935.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61522 AN: 151750 Hom.: 12594 Cov.: 31

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.406 AC: 61601 AN: 151866 Hom.: 12623 Cov.: 31 AF XY: 0.407 AC XY: 30212 AN XY: 74214

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.403

Gnomad4 EAS AF: 0.395

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.402

Alfa AF: 0.424 Hom.: 7329

Bravo AF: 0.393

Asia WGS AF: 0.484 AC: 1687 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.67
DANN	Benign	0.38

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs228918; hg19: chr22-37506680;