rs7156144

Variant names:

• chr14-67512996-G-A
• rs7156144
• NM_001348544.2:c.-257+2090C>T

Variant summary

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

The NM_182526.3(TMEM229B):​c.-192+2090C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 151,986 control chromosomes in the GnomAD database, including 10,137 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 0.35 (10137 hom., cov: 32)
• Consequence: TMEM229B NM_182526.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502

Genes affected

TMEM229B (HGNC:20130): (transmembrane protein 229B) Predicted to act upstream of or within response to bacterium. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

GPHN (HGNC:15465): (gephyrin) This gene encodes a neuronal assembly protein that anchors inhibitory neurotransmitter receptors to the postsynaptic cytoskeleton via high affinity binding to a receptor subunit domain and tubulin dimers. In nonneuronal tissues, the encoded protein is also required for molybdenum cofactor biosynthesis. Mutations in this gene may be associated with the neurological condition hyperplexia and also lead to molybdenum cofactor deficiency. Numerous alternatively spliced transcript variants encoding different isoforms have been described; however, the full-length nature of all transcript variants is not currently known. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM229B	NM_001348544.2	c.-257+2090C>T		intron_variant	Intron 1 of 3		NP_001335473.1
TMEM229B	NM_001348546.2	c.-192+20766C>T		intron_variant	Intron 1 of 2		NP_001335475.1
TMEM229B	NM_001348547.2	c.-192+20640C>T		intron_variant	Intron 1 of 2		NP_001335476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM229B	ENST00000357461.7	c.-192+2090C>T		intron_variant	Intron 1 of 2	2		ENSP00000350050.2
TMEM229B	ENST00000554278.6	c.-192+20640C>T		intron_variant	Intron 1 of 2	4		ENSP00000452402.2
TMEM229B	ENST00000555994.6	c.-257+2090C>T		intron_variant	Intron 1 of 3	3		ENSP00000452144.2

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53063 AN: 151868 Hom.: 10133 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.334

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

GnomAD4 genome AF: 0.349 AC: 53068 AN: 151986 Hom.: 10137 Cov.: 32 AF XY: 0.352 AC XY: 26163 AN XY: 74294

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.366

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.330

Alfa AF: 0.383 Hom.: 2054

Bravo AF: 0.345

Asia WGS AF: 0.355 AC: 1237 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.37

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: rs7156144; hg19: chr14-67979713;