rs12052523

Positions:

• chr2-227379681-G-A

Variant summary

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

The ENST00000449706.1(TM4SF20):​c.-92-321C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 152,000 control chromosomes in the GnomAD database, including 10,157 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 0.36 (10157 hom., cov: 34)
• Consequence: TM4SF20 ENST00000449706.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.258

Genes affected

TM4SF20 (HGNC:26230): (transmembrane 4 L six family member 20) The protein encoded by this gene is a member of the four-transmembrane L6 superfamily. Members of this family function in various cellular processes including cell proliferation, motility, and adhesion via their interactions with integrins. In human brain tissue, this gene is expressed at high levels in the parietal lobe, occipital lobe, hippocampus, pons, white matter, corpus callosum, and cerebellum. Knockout of the homologous gene in mouse results in a neurobehavioral phenotype with suggested enhanced motor coordination. A deletion mutation in the human gene is associated with specific language impairment-5. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TM4SF20	XM_011511876.3	c.-205+1908C>T		intron_variant			XP_011510178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TM4SF20	ENST00000449706.1	c.-92-321C>T		intron_variant		4		ENSP00000416565.1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55177 AN: 151882 Hom.: 10144 Cov.: 34

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.363 AC: 55221 AN: 152000 Hom.: 10157 Cov.: 34 AF XY: 0.363 AC XY: 26998 AN XY: 74296

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.319

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.427

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.335

Alfa AF: 0.386 Hom.: 8634

Bravo AF: 0.352

Asia WGS AF: 0.350 AC: 1216 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12052523; hg19: chr2-228244397;