rs4408717

Variant names:

• chr2-227367730-G-C
• rs4408717
• NM_024795.4:c.250-1486C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024795.4(TM4SF20):​c.250-1486C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,092 control chromosomes in the GnomAD database, including 2,271 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 0.11 (2271 hom., cov: 31)
• Consequence: TM4SF20 NM_024795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800
• Publications: 1 publications found

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]

TM4SF20 Gene-Disease associations (from GenCC):

• specific language impairment 5

  Inheritance: AD Classification: LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TM4SF20	NM_024795.4	c.250-1486C>G		intron_variant	Intron 2 of 3	ENST00000304568.4	NP_079071.2
TM4SF20	XM_011511876.3	c.49-1486C>G		intron_variant	Intron 3 of 4		XP_011510178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TM4SF20	ENST00000304568.4	c.250-1486C>G		intron_variant	Intron 2 of 3	1	NM_024795.4	ENSP00000303028.3

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16362 AN: 151974 Hom.: 2256 Cov.: 31

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0483

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.0710

Gnomad FIN AF: 0.0426

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0105

Gnomad OTH AF: 0.0852

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

GnomAD4 genome AF: 0.108 AC: 16412 AN: 152092 Hom.: 2271 Cov.: 31 AF XY: 0.109 AC XY: 8079 AN XY: 74390

African (AFR) AF: 0.318 AC: 13161 AN: 41416

American (AMR) AF: 0.0483 AC: 738 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0323 AC: 112 AN: 3470

East Asian (EAS) AF: 0.135 AC: 696 AN: 5170

South Asian (SAS) AF: 0.0702 AC: 339 AN: 4826

European-Finnish (FIN) AF: 0.0426 AC: 452 AN: 10602

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0105 AC: 711 AN: 68002

Other (OTH) AF: 0.0848 AC: 179 AN: 2112

Alfa AF: 0.0647 Hom.: 154

Bravo AF: 0.118

Asia WGS AF: 0.122 AC: 425 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.44
PhyloP100		0.0080
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4408717; hg19: chr2-228232446; COSMIC: COSV107350002;