rs4142495

Variant names:

• chr9-35728497-G-A
• rs4142495
• NM_006289.4:c.-33-2770C>T

Variant summary

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

The NM_006289.4(TLN1):​c.-33-2770C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 151,682 control chromosomes in the GnomAD database, including 10,343 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 (10343 hom., cov: 31)
• Consequence: TLN1 NM_006289.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.717
• Publications: 11 publications found

Genes affected

TLN1 (HGNC:11845): (talin 1) This gene encodes a cytoskeletal protein that is concentrated in areas of cell-substratum and cell-cell contacts. The encoded protein plays a significant role in the assembly of actin filaments and in spreading and migration of various cell types, including fibroblasts and osteoclasts. It codistributes with integrins in the cell surface membrane in order to assist in the attachment of adherent cells to extracellular matrices and of lymphocytes to other cells. The N-terminus of this protein contains elements for localization to cell-extracellular matrix junctions. The C-terminus contains binding sites for proteins such as beta-1-integrin, actin, and vinculin. [provided by RefSeq, Feb 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLN1	NM_006289.4	c.-33-2770C>T		intron_variant	Intron 1 of 56	ENST00000314888.10	NP_006280.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLN1	ENST00000314888.10	c.-33-2770C>T		intron_variant	Intron 1 of 56	1	NM_006289.4	ENSP00000316029.9
TLN1	ENST00000706939.1	c.-33-2770C>T		intron_variant	Intron 1 of 57			ENSP00000516659.1
TLN1	ENST00000378192.2	n.31-2770C>T		intron_variant	Intron 1 of 6	2

Frequencies

GnomAD3 genomes AF: 0.356 AC: 53997 AN: 151564 Hom.: 10316 Cov.: 31

Gnomad AFR AF: 0.493

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.356 AC: 54055 AN: 151682 Hom.: 10343 Cov.: 31 AF XY: 0.353 AC XY: 26165 AN XY: 74146

African (AFR) AF: 0.493 AC: 20376 AN: 41292

American (AMR) AF: 0.342 AC: 5213 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1091 AN: 3472

East Asian (EAS) AF: 0.384 AC: 1982 AN: 5156

South Asian (SAS) AF: 0.222 AC: 1064 AN: 4802

European-Finnish (FIN) AF: 0.277 AC: 2923 AN: 10534

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20467 AN: 67878

Other (OTH) AF: 0.318 AC: 668 AN: 2102

Alfa AF: 0.322 Hom.: 3196

Bravo AF: 0.368

Asia WGS AF: 0.282 AC: 980 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.2
DANN	Benign	0.47
PhyloP100		-0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs4142495; hg19: chr9-35728494;