rs1020004

Positions:

• chr7-12216152-T-C

Variant summary

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

The NM_001134232.2(TMEM106B):​c.217+1125T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 151,978 control chromosomes in the GnomAD database, including 6,432 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 0.29 (6432 hom., cov: 31)
• Consequence: TMEM106B NM_001134232.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0480

Genes affected

TMEM106B (HGNC:22407): (transmembrane protein 106B) Enables ATPase binding activity. Involved in dendrite morphogenesis and lysosome localization. Located in endosome and lysosomal membrane. Implicated in hypomyelinating leukodystrophy. [provided by Alliance of Genome Resources, Apr 2022]

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 (SAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM106B	NM_001134232.2	c.217+1125T>C		intron_variant		ENST00000396668.8	NP_001127704.1
TMEM106B	NM_018374.4	c.217+1125T>C		intron_variant			NP_060844.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM106B	ENST00000396668.8	c.217+1125T>C		intron_variant		1	NM_001134232.2	ENSP00000379902	P1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43559 AN: 151858 Hom.: 6432 Cov.: 31

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.287 AC: 43580 AN: 151978 Hom.: 6432 Cov.: 31 AF XY: 0.287 AC XY: 21296 AN XY: 74276

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.341

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.283

Alfa AF: 0.317 Hom.: 3553

Bravo AF: 0.282

Asia WGS AF: 0.368 AC: 1279 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	5.5
DANN	Benign	0.62

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: rs1020004; hg19: chr7-12255778;