9-35723715-T-C

Position:

• chr9-35723715-T-C

Variant summary

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

The NM_006289.4(TLN1):​c.782+237A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 506,174 control chromosomes in the GnomAD database, including 17,665 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 0.22 (4340 hom., cov: 32)
  • Exomes 𝑓: 0.27 (13325 hom.)
• Consequence: TLN1 NM_006289.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

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]

TLN1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLN1	NM_006289.4	c.782+237A>G		intron_variant		ENST00000314888.10	NP_006280.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLN1	ENST00000314888.10	c.782+237A>G		intron_variant		1	NM_006289.4	ENSP00000316029.9
TLN1	ENST00000706939.1	c.782+237A>G		intron_variant				ENSP00000516659.1
TLN1	ENST00000378192.2	n.1082A>G		non_coding_transcript_exon_variant	7/7	2

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32796 AN: 151822 Hom.: 4345 Cov.: 32

Gnomad AFR AF: 0.0614

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.266 AC: 94243 AN: 354234 Hom.: 13325 Cov.: 6 AF XY: 0.262 AC XY: 48533 AN XY: 185086

Gnomad4 AFR exome AF: 0.0538

Gnomad4 AMR exome AF: 0.282

Gnomad4 ASJ exome AF: 0.263

Gnomad4 EAS exome AF: 0.331

Gnomad4 SAS exome AF: 0.184

Gnomad4 FIN exome AF: 0.241

Gnomad4 NFE exome AF: 0.284

Gnomad4 OTH exome AF: 0.259

GnomAD4 genome AF: 0.216 AC: 32768 AN: 151940 Hom.: 4340 Cov.: 32 AF XY: 0.216 AC XY: 16018 AN XY: 74254

Gnomad4 AFR AF: 0.0612

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.219

Alfa AF: 0.227 Hom.: 752

Bravo AF: 0.214

Asia WGS AF: 0.218 AC: 756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.66

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: rs1534847; hg19: chr9-35723712;