14-67512996-G-A

Position:

• chr14-67512996-G-A

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:):

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/exons	MANE	Protein	UniProt
TMEM229B	NM_001348544.2	c.-257+2090C>T		intron_variant			NP_001335473.1
TMEM229B	NM_001348546.2	c.-192+20766C>T		intron_variant			NP_001335475.1
TMEM229B	NM_001348547.2	c.-192+20640C>T		intron_variant			NP_001335476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM229B	ENST00000357461.7	c.-192+2090C>T		intron_variant		2		ENSP00000350050	P1
TMEM229B	ENST00000554278.6	c.-192+20640C>T		intron_variant		4		ENSP00000452402	P1
TMEM229B	ENST00000555994.6	c.-257+2090C>T		intron_variant		3		ENSP00000452144	P1

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;