rs7633016

Positions:

• chr3-46687169-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_147129.5(ALS2CL):​c.369-21C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 1,516,756 control chromosomes in the GnomAD database, including 90,649 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.43 (15733 hom., cov: 32)
  • Exomes 𝑓: 0.32 (74916 hom.)
• Consequence: ALS2CL NM_147129.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.843

Genes affected

ALS2CL (HGNC:20605): (ALS2 C-terminal like) Enables identical protein binding activity. Acts upstream of or within endosome organization. Predicted to be located in cytoplasmic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ALS2CL (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALS2CL	NM_147129.5	c.369-21C>T		intron_variant		ENST00000318962.9	NP_667340.2
ALS2CL	NM_001190707.2	c.369-21C>T		intron_variant			NP_001177636.1
ALS2CL	NR_033815.3	n.431-21C>T		intron_variant
ALS2CL	NR_135622.2	n.431-21C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALS2CL	ENST00000318962.9	c.369-21C>T		intron_variant		1	NM_147129.5	ENSP00000313670.4

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64533 AN: 151636 Hom.: 15723 Cov.: 32

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.424

GnomAD3 exomes AF: 0.371 AC: 54877 AN: 147730 Hom.: 10739 AF XY: 0.367 AC XY: 29272 AN XY: 79846

Gnomad AFR exome AF: 0.692

Gnomad AMR exome AF: 0.404

Gnomad ASJ exome AF: 0.357

Gnomad EAS exome AF: 0.285

Gnomad SAS exome AF: 0.387

Gnomad FIN exome AF: 0.335

Gnomad NFE exome AF: 0.325

Gnomad OTH exome AF: 0.350

GnomAD4 exome AF: 0.324 AC: 442297 AN: 1365002 Hom.: 74916 Cov.: 33 AF XY: 0.325 AC XY: 218396 AN XY: 671512

Gnomad4 AFR exome AF: 0.695

Gnomad4 AMR exome AF: 0.397

Gnomad4 ASJ exome AF: 0.337

Gnomad4 EAS exome AF: 0.282

Gnomad4 SAS exome AF: 0.379

Gnomad4 FIN exome AF: 0.326

Gnomad4 NFE exome AF: 0.306

Gnomad4 OTH exome AF: 0.347

GnomAD4 genome AF: 0.426 AC: 64586 AN: 151754 Hom.: 15733 Cov.: 32 AF XY: 0.425 AC XY: 31499 AN XY: 74142

Gnomad4 AFR AF: 0.682

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.288

Gnomad4 SAS AF: 0.383

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.419

Alfa AF: 0.333 Hom.: 14209

Bravo AF: 0.444

Asia WGS AF: 0.331 AC: 1153 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.17
DANN	Benign	0.60

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: rs7633016; hg19: chr3-46728659; COSMIC: COSV59670037;