Genetic Variant ECSIT:c.738+6C>T (chr19-11513050-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_016581.5(ECSIT):c.738+6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00898 in 1,613,306 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0062 ( 6 hom., cov: 31)

Exomes 𝑓: 0.0093 ( 81 hom. )

Consequence

ECSIT
NM_016581.5 splice_region, intron

Scores

Splicing: ADA: 0.00004162

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.01

Variant links:

Genes affected

ECSIT (HGNC:29548): (ECSIT signaling integrator) Predicted to enable DNA-binding transcription factor activity and chromatin binding activity. Involved in regulation of oxidoreductase activity and regulation of protein complex stability. Located in cytosol; mitochondrion; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ECSIT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 19-11513050-G-A is Benign according to our data. Variant chr19-11513050-G-A is described in ClinVar as [Benign]. Clinvar id is 2649334.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ECSIT	NM_016581.5 link	c.738+6C>T	splice_region_variant, intron_variant	Intron 4 of 7	ENST00000270517.12	NP_057665.2	Q9BQ95-1
ECSIT	NM_001142464.3 link	c.738+6C>T	splice_region_variant, intron_variant	Intron 4 of 6		NP_001135936.1	Q9BQ95-2
ECSIT	NM_001243204.2 link	c.738+6C>T	splice_region_variant, intron_variant	Intron 4 of 7		NP_001230133.1	Q9BQ95-4
ECSIT	NM_001142465.3 link	c.97-5002C>T	intron_variant	Intron 2 of 5		NP_001135937.1	Q9BQ95-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECSIT	ENST00000270517.12 link	c.738+6C>T		splice_region_variant, intron_variant	Intron 4 of 7	1	NM_016581.5	ENSP00000270517.6		Q9BQ95-1

Frequencies

GnomAD3 genomes

AF:

0.00624

AC:

950

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00207

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.00656

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00994

Gnomad OTH

AF:

0.00909

GnomAD3 exomes

AF:

0.00576

AC:

1438

AN:

249816

Hom.:

AF XY:

0.00544

AC XY:

737

AN XY:

135354

show subpopulations

Gnomad AFR exome

AF:

0.00182

Gnomad AMR exome

AF:

0.00385

Gnomad ASJ exome

AF:

0.00369

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000653

Gnomad FIN exome

AF:

0.00328

Gnomad NFE exome

AF:

0.00985

Gnomad OTH exome

AF:

0.00638

GnomAD4 exome

AF:

0.00927

AC:

13543

AN:

1460994

Hom.:

Cov.:

AF XY:

0.00901

AC XY:

6551

AN XY:

726802

show subpopulations

Gnomad4 AFR exome

AF:

0.00161

Gnomad4 AMR exome

AF:

0.00380

Gnomad4 ASJ exome

AF:

0.00352

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000661

Gnomad4 FIN exome

AF:

0.00305

Gnomad4 NFE exome

AF:

0.0113

Gnomad4 OTH exome

AF:

0.00716

GnomAD4 genome

AF:

0.00624

AC:

951

AN:

152312

Hom.:

Cov.:

AF XY:

0.00616

AC XY:

459

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00207

Gnomad4 AMR

AF:

0.00655

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00245

Gnomad4 NFE

AF:

0.00994

Gnomad4 OTH

AF:

0.00947

Alfa

AF:

0.00726

Hom.:

Bravo

AF:

0.00640

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00785

EpiControl

AF:

0.00866

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ECSIT: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.62

DANN

Benign

0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000042

dbscSNV1_RF

Benign

0.016

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

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