1-18872187-GC-G

Position:

• chr1-18872187-GC-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_003748.4(ALDH4A1):​c.*657del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (13599 hom., cov: 0)
  • Exomes 𝑓: 0.45 (35 hom.)
• Consequence: ALDH4A1 NM_003748.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.28

Genes affected

ALDH4A1 (HGNC:406): (aldehyde dehydrogenase 4 family member A1) This protein belongs to the aldehyde dehydrogenase family of proteins. This enzyme is a mitochondrial matrix NAD-dependent dehydrogenase which catalyzes the second step of the proline degradation pathway, converting pyrroline-5-carboxylate to glutamate. Deficiency of this enzyme is associated with type II hyperprolinemia, an autosomal recessive disorder characterized by accumulation of delta-1-pyrroline-5-carboxylate (P5C) and proline. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jun 2009]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-18872187-GC-G is Benign according to our data. Variant chr1-18872187-GC-G is described in ClinVar as [Likely_benign]. Clinvar id is 294349.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH4A1	NM_003748.4	c.*657del		3_prime_UTR_variant	15/15	ENST00000375341.8
ALDH4A1	NM_001161504.2	c.*657del		3_prime_UTR_variant	15/15
ALDH4A1	NM_001319218.2	c.*657del		3_prime_UTR_variant	14/14
ALDH4A1	NM_170726.3	c.*42-398del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH4A1	ENST00000375341.8	c.*657del		3_prime_UTR_variant	15/15	1	NM_003748.4	P1
ALDH4A1	ENST00000538839.5	c.*657del		3_prime_UTR_variant	14/14	1
ALDH4A1	ENST00000290597.9	c.*42-398del		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61929 AN: 152054 Hom.: 13583 Cov.: 0

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.427

GnomAD4 exome AF: 0.454 AC: 127 AN: 280 Hom.: 35 Cov.: 0 AF XY: 0.486 AC XY: 105 AN XY: 216

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.667

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.446

Gnomad4 OTH exome AF: 0.583

GnomAD4 genome AF: 0.407 AC: 61978 AN: 152172 Hom.: 13599 Cov.: 0 AF XY: 0.416 AC XY: 30933 AN XY: 74382

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.529

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.685

Gnomad4 SAS AF: 0.601

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.427

Alfa AF: 0.277 Hom.: 687

Bravo AF: 0.406

Asia WGS AF: 0.603 AC: 2095 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hyperprolinemia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs11311839; hg19: chr1-19198681;