Variant 12-124947898-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_032656.4(DHX37):c.3389-11C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 1,610,286 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0087 ( 12 hom., cov: 34)

Exomes 𝑓: 0.012 ( 107 hom. )

Consequence

DHX37
NM_032656.4 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00003510

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.445

Variant links:

Genes affected

DHX37 (HGNC:17210): (DEAH-box helicase 37) This gene encodes a DEAD box protein. DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. [provided by RefSeq, Jul 2008]

DHX37 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 12-124947898-G-A is Benign according to our data. Variant chr12-124947898-G-A is described in ClinVar as [Benign]. Clinvar id is 1971107.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00875 (1333/152344) while in subpopulation NFE AF= 0.0135 (917/68026). AF 95% confidence interval is 0.0128. There are 12 homozygotes in gnomad4. There are 570 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHX37	NM_032656.4 linkuse as main transcript	c.3389-11C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000308736.7	NP_116045.2
DHX37	XM_005253590.4 linkuse as main transcript			downstream_gene_variant			XP_005253647.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
DHX37	ENST00000544745.2 linkuse as main transcript	c.*46C>T	3_prime_UTR_variant	23/23	1		ENSP00000439009
DHX37	ENST00000308736.7 linkuse as main transcript	c.3389-11C>T	splice_polypyrimidine_tract_variant, intron_variant		1	NM_032656.4	ENSP00000311135	P1
DHX37	ENST00000507267.2 linkuse as main transcript	n.533-11C>T	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		1
DHX37	ENST00000542400.5 linkuse as main transcript	n.2003-11C>T	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00876

AC:

1334

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00514

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00687

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00282

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0135

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.00856

AC:

2098

AN:

245172

Hom.:

AF XY:

0.00861

AC XY:

1141

AN XY:

132462

show subpopulations

Gnomad AFR exome

AF:

0.00516

Gnomad AMR exome

AF:

0.00765

Gnomad ASJ exome

AF:

0.00220

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00263

Gnomad FIN exome

AF:

0.00304

Gnomad NFE exome

AF:

0.0138

Gnomad OTH exome

AF:

0.0129

GnomAD4 exome

AF:

0.0120

AC:

17499

AN:

1457942

Hom.:

107

Cov.:

AF XY:

0.0118

AC XY:

8550

AN XY:

724726

show subpopulations

Gnomad4 AFR exome

AF:

0.00553

Gnomad4 AMR exome

AF:

0.00803

Gnomad4 ASJ exome

AF:

0.00202

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00240

Gnomad4 FIN exome

AF:

0.00310

Gnomad4 NFE exome

AF:

0.0141

Gnomad4 OTH exome

AF:

0.0113

GnomAD4 genome

AF:

0.00875

AC:

1333

AN:

152344

Hom.:

Cov.:

AF XY:

0.00765

AC XY:

570

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00510

Gnomad4 AMR

AF:

0.00686

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.00282

Gnomad4 NFE

AF:

0.0135

Gnomad4 OTH

AF:

0.0165

Alfa

AF:

0.0101

Hom.:

Bravo

AF:

0.00914

Asia WGS

AF:

0.00260

AC:

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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

6.2

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000035

dbscSNV1_RF

Benign

0.094

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