rs228907

Positions:

• chr22-37101553-G-A
• chr22-37101553-G-C

Variant summary

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

The NM_001374504.1(TMPRSS6):​c.202+1663C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 151,792 control chromosomes in the GnomAD database, including 8,352 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 0.33 (8352 hom., cov: 31)
• Consequence: TMPRSS6 NM_001374504.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.850

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMPRSS6	NM_001374504.1	c.202+1663C>T		intron_variant		ENST00000676104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMPRSS6	ENST00000676104.1	c.202+1663C>T		intron_variant			NM_001374504.1	P1

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49382 AN: 151674 Hom.: 8337 Cov.: 31

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.326 AC: 49442 AN: 151792 Hom.: 8352 Cov.: 31 AF XY: 0.326 AC XY: 24180 AN XY: 74184

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.305

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.307

Alfa AF: 0.278 Hom.: 8640

Bravo AF: 0.322

Asia WGS AF: 0.449 AC: 1562 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs228907; hg19: chr22-37497593;