rs228919

Variant names:

• chr22-37110673-G-T
• rs228919
• ENST00000723443.1:n.296G>T

Variant summary

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

The ENST00000723443.1(ENSG00000294412):​n.296G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 151,620 control chromosomes in the GnomAD database, including 12,581 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 (12581 hom., cov: 31)
• Consequence: ENSG00000294412 ENST00000723443.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 7 publications found

Genes affected

ENSG00000294412 (HGNC:):

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]

TMPRSS6 Gene-Disease associations (from GenCC):

• IRIDA syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -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 = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS6	XM_024452167.2	c.-220C>A		upstream_gene_variant			XP_024307935.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000294412	ENST00000723443.1	n.296G>T		non_coding_transcript_exon_variant	Exon 2 of 2
ENSG00000294412	ENST00000723444.1	n.477G>T		non_coding_transcript_exon_variant	Exon 2 of 2
ENSG00000294412	ENST00000723445.1	n.673G>T		non_coding_transcript_exon_variant	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61405 AN: 151512 Hom.: 12553 Cov.: 31

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.401

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: 0.405 AC: 61481 AN: 151620 Hom.: 12581 Cov.: 31 AF XY: 0.407 AC XY: 30138 AN XY: 74078

African (AFR) AF: 0.386 AC: 15950 AN: 41330

American (AMR) AF: 0.339 AC: 5161 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1397 AN: 3468

East Asian (EAS) AF: 0.393 AC: 2029 AN: 5158

South Asian (SAS) AF: 0.486 AC: 2339 AN: 4810

European-Finnish (FIN) AF: 0.440 AC: 4593 AN: 10432

Middle Eastern (MID) AF: 0.397 AC: 116 AN: 292

European-Non Finnish (NFE) AF: 0.424 AC: 28777 AN: 67874

Other (OTH) AF: 0.403 AC: 847 AN: 2102

Alfa AF: 0.412 Hom.: 5107

Bravo AF: 0.392

Asia WGS AF: 0.483 AC: 1683 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	0.33
DANN	Benign	0.29
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs228919; hg19: chr22-37506713;