chr17-7219637-G-A

Variant names:

• chr17-7219637-G-A
• rs79809891
• ENST00000491753.2:n.-788C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000491753.2(DLG4):​n.-788C>T variant causes a non coding transcript exon 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 ENST00000491753.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.37
• Publications: 2 publications found

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]

ACADVL Gene-Disease associations (from GenCC):

• very long chain acyl-CoA dehydrogenase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DLG4	NR_135527.1	n.414C>T		non_coding_transcript_exon_variant	Exon 1 of 21
DLG4	NM_001365.5	c.-788C>T		5_prime_UTR_variant	Exon 1 of 22		NP_001356.1
DLG4	NM_001321074.1	c.-788C>T		5_prime_UTR_variant	Exon 1 of 22		NP_001308003.1
ACADVL	NM_001270447.2	c.132-485G>A		intron_variant	Intron 2 of 20		NP_001257376.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG4	ENST00000491753.2	n.-788C>T		non_coding_transcript_exon_variant	Exon 1 of 21	2		ENSP00000467897.2
DLG4	ENST00000648172.9	c.-788C>T		5_prime_UTR_variant	Exon 1 of 22			ENSP00000497806.3
DLG4	ENST00000491753.2	n.-788C>T		5_prime_UTR_variant	Exon 1 of 21	2		ENSP00000467897.2

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

African (AFR) AF: 0.0977 AC: 2245 AN: 22978

American (AMR) AF: 0.00751 AC: 96 AN: 12780

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12532

East Asian (EAS) AF: 0.00 AC: 0 AN: 18450

South Asian (SAS) AF: 0.000197 AC: 10 AN: 50840

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13606

Middle Eastern (MID) AF: 0.00367 AC: 10 AN: 2724

European-Non Finnish (NFE) AF: 0.0000867 AC: 79 AN: 911272

Other (OTH) AF: 0.00485 AC: 205 AN: 42228

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

African (AFR) AF: 0.0946 AC: 3923 AN: 41474

American (AMR) AF: 0.0112 AC: 171 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000324 AC: 22 AN: 68006

Other (OTH) AF: 0.0251 AC: 53 AN: 2110

Alfa AF: 0.0151 Hom.: 27

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

Jun 28, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	13
DANN	Benign	0.51
PhyloP100		1.4
PromoterAI		0.0024	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs79809891; hg19: chr17-7122956;