Variant 22-23614135-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_016449.4(DRICH1):c.621C>T(p.His207His) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00776 in 1,606,536 control chromosomes in the GnomAD database, including 68 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0055 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0080 ( 66 hom. )

Consequence

DRICH1
NM_016449.4 splice_region, synonymous

Scores

Splicing: ADA: 0.0009027

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.69

Variant links:

Genes affected

DRICH1 (HGNC:28031): (aspartate rich 1)

DRICH1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.09).

BP6

Variant 22-23614135-G-A is Benign according to our data. Variant chr22-23614135-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2652966.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.68 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRICH1	NM_016449.4 linkuse as main transcript	c.621C>T	p.His207His	splice_region_variant, synonymous_variant	9/12	ENST00000317749.9	NP_057533.2	Q6PGQ1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRICH1	ENST00000317749.9 linkuse as main transcript	c.621C>T	p.His207His	splice_region_variant, synonymous_variant	9/12	1	NM_016449.4	ENSP00000316137.5		Q6PGQ1

Frequencies

GnomAD3 genomes

AF:

0.00553

AC:

841

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00366

Gnomad ASJ

AF:

0.0213

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00891

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00581

AC:

1450

AN:

249356

Hom.:

AF XY:

0.00577

AC XY:

780

AN XY:

135288

show subpopulations

Gnomad AFR exome

AF:

0.00136

Gnomad AMR exome

AF:

0.00305

Gnomad ASJ exome

AF:

0.0167

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00128

Gnomad FIN exome

AF:

0.00436

Gnomad NFE exome

AF:

0.00862

Gnomad OTH exome

AF:

0.00777

GnomAD4 exome

AF:

0.00799

AC:

11621

AN:

1454234

Hom.:

Cov.:

AF XY:

0.00788

AC XY:

5705

AN XY:

723980

show subpopulations

Gnomad4 AFR exome

AF:

0.00126

Gnomad4 AMR exome

AF:

0.00282

Gnomad4 ASJ exome

AF:

0.0172

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00122

Gnomad4 FIN exome

AF:

0.00477

Gnomad4 NFE exome

AF:

0.00921

Gnomad4 OTH exome

AF:

0.00773

GnomAD4 genome

AF:

0.00552

AC:

841

AN:

152302

Hom.:

Cov.:

AF XY:

0.00498

AC XY:

371

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.00366

Gnomad4 ASJ

AF:

0.0213

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00377

Gnomad4 NFE

AF:

0.00891

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00883

Hom.:

Bravo

AF:

0.00532

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00785

EpiControl

AF:

0.00782

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2024

DRICH1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.45

DANN

Benign

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00090

dbscSNV1_RF

Benign

0.54

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