Variant chr7-19116526-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000474.4(TWIST1):c.*42+145G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0533 in 714,670 control chromosomes in the GnomAD database, including 1,570 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.053 ( 283 hom., cov: 32)

Exomes 𝑓: 0.053 ( 1287 hom. )

Consequence

TWIST1
NM_000474.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.251

Variant links:

Genes affected

TWIST1 (HGNC:12428): (twist family bHLH transcription factor 1) This gene encodes a basic helix-loop-helix (bHLH) transcription factor that plays an important role in embryonic development. The encoded protein forms both homodimers and heterodimers that bind to DNA E box sequences and regulate the transcription of genes involved in cranial suture closure during skull development. This protein may also regulate neural tube closure, limb development and brown fat metabolism. This gene is hypermethylated and overexpressed in multiple human cancers, and the encoded protein promotes tumor cell invasion and metastasis, as well as metastatic recurrence. Mutations in this gene cause Saethre-Chotzen syndrome in human patients, which is characterized by craniosynostosis, ptosis and hypertelorism. [provided by RefSeq, Jul 2020]

TWIST1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 7-19116526-C-A is Benign according to our data. Variant chr7-19116526-C-A is described in ClinVar as [Benign]. Clinvar id is 1272414.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TWIST1	NM_000474.4 linkuse as main transcript	c.*42+145G>T		intron_variant		ENST00000242261.6
TWIST1	NR_149001.2 linkuse as main transcript	n.966+145G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
TWIST1	ENST00000242261.6 linkuse as main transcript	c.*42+145G>T	intron_variant	1	NM_000474.4	P1
TWIST1	ENST00000354571.5 linkuse as main transcript	c.*42+145G>T	intron_variant, NMD_transcript_variant	2
TWIST1	ENST00000443687.5 linkuse as main transcript	c.*42+145G>T	intron_variant, NMD_transcript_variant	4

Frequencies

GnomAD3 genomes

AF:

0.0530

AC:

8064

AN:

152028

Hom.:

282

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0672

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.0495

Gnomad ASJ

AF:

0.0646

Gnomad EAS

AF:

0.122

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.0382

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0378

Gnomad OTH

AF:

0.0447

GnomAD4 exome

AF:

0.0534

AC:

30052

AN:

562524

Hom.:

1287

AF XY:

0.0558

AC XY:

16270

AN XY:

291458

show subpopulations

Gnomad4 AFR exome

AF:

0.0640

Gnomad4 AMR exome

AF:

0.0477

Gnomad4 ASJ exome

AF:

0.0640

Gnomad4 EAS exome

AF:

0.178

Gnomad4 SAS exome

AF:

0.103

Gnomad4 FIN exome

AF:

0.0294

Gnomad4 NFE exome

AF:

0.0377

Gnomad4 OTH exome

AF:

0.0508

GnomAD4 genome

AF:

0.0531

AC:

8072

AN:

152146

Hom.:

283

Cov.:

AF XY:

0.0542

AC XY:

4034

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0671

Gnomad4 AMR

AF:

0.0495

Gnomad4 ASJ

AF:

0.0646

Gnomad4 EAS

AF:

0.122

Gnomad4 SAS

AF:

0.102

Gnomad4 FIN

AF:

0.0382

Gnomad4 NFE

AF:

0.0377

Gnomad4 OTH

AF:

0.0442

Alfa

AF:

0.0412

Hom.:

Bravo

AF:

0.0542

Asia WGS

AF:

0.105

AC:

362

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.1

DANN

Benign

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over