chr17-7219637-G-A

Position:

• chr17-7219637-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000399510.8(DLG4):​c.-788C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0055 in 1,239,582 control chromosomes in the GnomAD database, including 316 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (192 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (124 hom.)
• Consequence: DLG4 ENST00000399510.8 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.37

Genes affected

DLG4 (HGNC:2903): (discs large MAGUK scaffold protein 4) This gene encodes a member of the membrane-associated guanylate kinase (MAGUK) family. It heteromultimerizes with another MAGUK protein, DLG2, and is recruited into NMDA receptor and potassium channel clusters. These two MAGUK proteins may interact at postsynaptic sites to form a multimeric scaffold for the clustering of receptors, ion channels, and associated signaling proteins. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACADVL (HGNC:92): (acyl-CoA dehydrogenase very long chain) The protein encoded by this gene is targeted to the inner mitochondrial membrane where it catalyzes the first step of the mitochondrial fatty acid beta-oxidation pathway. This acyl-Coenzyme A dehydrogenase is specific to long-chain and very-long-chain fatty acids. A deficiency in this gene product reduces myocardial fatty acid beta-oxidation and is associated with cardiomyopathy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 17-7219637-G-A is Benign according to our data. Variant chr17-7219637-G-A is described in ClinVar as [Benign]. Clinvar id is 1246043.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLG4	NM_001321074.1	c.-788C>T		5_prime_UTR_variant	1/22
DLG4	NM_001365.4	c.-788C>T		5_prime_UTR_variant	1/22
ACADVL	NM_001270447.2	c.132-485G>A		intron_variant
DLG4	NR_135527.1	n.414C>T		non_coding_transcript_exon_variant	1/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLG4	ENST00000399510.8	c.-788C>T		5_prime_UTR_variant	1/22	1
DLG4	ENST00000648172.8	c.-788C>T		5_prime_UTR_variant	1/22
ACADVL	ENST00000543245.6	c.132-485G>A		intron_variant		2
DLG4	ENST00000491753.2	c.-788C>T		5_prime_UTR_variant, NMD_transcript_variant	1/21	2

Frequencies

GnomAD3 genomes AF: 0.0274 AC: 4163 AN: 152054 Hom.: 190 Cov.: 32

Gnomad AFR AF: 0.0947

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0112

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0254

GnomAD4 exome AF: 0.00243 AC: 2645 AN: 1087410 Hom.: 124 Cov.: 29 AF XY: 0.00223 AC XY: 1155 AN XY: 519000

Gnomad4 AFR exome AF: 0.0977

Gnomad4 AMR exome AF: 0.00751

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000197

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000867

Gnomad4 OTH exome AF: 0.00485

GnomAD4 genome AF: 0.0274 AC: 4170 AN: 152172 Hom.: 192 Cov.: 32 AF XY: 0.0257 AC XY: 1912 AN XY: 74414

Gnomad4 AFR AF: 0.0946

Gnomad4 AMR AF: 0.0112

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000324

Gnomad4 OTH AF: 0.0251

Alfa AF: 0.0203 Hom.: 15

Bravo AF: 0.0311

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	13
DANN	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs79809891; hg19: chr17-7122956;