rs228918

Variant names:

• chr22-37110640-T-C
• rs228918
• ENST00000723443.1:n.263T>C

Variant summary

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

The ENST00000723443.1(ENSG00000294412):​n.263T>C 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 0.406 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: ENSG00000294412 ENST00000723443.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.361
• Publications: 14 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 = 0.471 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
ENSG00000294412	ENST00000723443.1	n.263T>C		non_coding_transcript_exon_variant	Exon 2 of 2
ENSG00000294412	ENST00000723444.1	n.444T>C		non_coding_transcript_exon_variant	Exon 2 of 2
ENSG00000294412	ENST00000723445.1	n.640T>C		non_coding_transcript_exon_variant	Exon 2 of 2

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

African (AFR) AF: 0.387 AC: 16026 AN: 41404

American (AMR) AF: 0.338 AC: 5165 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1396 AN: 3466

East Asian (EAS) AF: 0.395 AC: 2046 AN: 5174

South Asian (SAS) AF: 0.487 AC: 2347 AN: 4820

European-Finnish (FIN) AF: 0.438 AC: 4601 AN: 10498

Middle Eastern (MID) AF: 0.401 AC: 117 AN: 292

European-Non Finnish (NFE) AF: 0.424 AC: 28782 AN: 67928

Other (OTH) AF: 0.402 AC: 849 AN: 2110

Alfa AF: 0.420 Hom.: 10160

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
PhyloP100		-0.36

Splicing

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

Other links and lift over

dbSNP: rs228918; hg19: chr22-37506680;