chr9-35700840-C-T

Variant names:

• chr9-35700840-C-T
• rs4879926
• NM_006289.4:c.6475-464G>A

Variant summary

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

The NM_006289.4(TLN1):​c.6475-464G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.929 in 152,300 control chromosomes in the GnomAD database, including 66,117 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 0.93 (66117 hom., cov: 33)
• Consequence: TLN1 NM_006289.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLN1	NM_006289.4	c.6475-464G>A		intron_variant	Intron 48 of 56	ENST00000314888.10	NP_006280.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLN1	ENST00000314888.10	c.6475-464G>A		intron_variant	Intron 48 of 56	1	NM_006289.4	ENSP00000316029.9
TLN1	ENST00000706939.1	c.6526-464G>A		intron_variant	Intron 49 of 57			ENSP00000516659.1

Frequencies

GnomAD3 genomes AF: 0.929 AC: 141319 AN: 152182 Hom.: 66071 Cov.: 33

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.978

Gnomad AMR AF: 0.971

Gnomad ASJ AF: 0.979

Gnomad EAS AF: 0.937

Gnomad SAS AF: 0.979

Gnomad FIN AF: 0.960

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.982

Gnomad OTH AF: 0.951

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

GnomAD4 genome AF: 0.929 AC: 141425 AN: 152300 Hom.: 66117 Cov.: 33 AF XY: 0.930 AC XY: 69241 AN XY: 74468

African (AFR) AF: 0.803 AC: 33338 AN: 41526

American (AMR) AF: 0.972 AC: 14872 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.979 AC: 3398 AN: 3472

East Asian (EAS) AF: 0.937 AC: 4860 AN: 5188

South Asian (SAS) AF: 0.979 AC: 4726 AN: 4828

European-Finnish (FIN) AF: 0.960 AC: 10196 AN: 10618

Middle Eastern (MID) AF: 0.973 AC: 286 AN: 294

European-Non Finnish (NFE) AF: 0.982 AC: 66846 AN: 68040

Other (OTH) AF: 0.951 AC: 2011 AN: 2114

Alfa AF: 0.966 Hom.: 313848

Bravo AF: 0.924

Asia WGS AF: 0.961 AC: 3342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.3
DANN	Benign	0.61
PhyloP100		-0.13
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: rs4879926; hg19: chr9-35700837;