chr4-148526433-T-C

Variant names:

• chr4-148526433-T-C
• rs10446758

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The variant allele was found at a frequency of 0.491 in 606,578 control chromosomes in the GnomAD database, including 77,805 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 0.44 (16130 hom., cov: 29)
  • Exomes 𝑓: 0.51 (61675 hom.)
• Consequence: ASS1P8 intragenic
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21
• Publications: 2 publications found

Genes affected

ASS1P8 (HGNC:771): (argininosuccinate synthetase 1 pseudogene 8)

ENSG00000287292 (HGNC:58892):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000661928.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000287292	ENST00000661928.1		n.105-18034T>C		intron	N/A
	ENSG00000287292	ENST00000669991.1		n.169-18031T>C		intron	N/A
	ENSG00000287292	ENST00000817567.1		n.250-18031T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66622 AN: 151474 Hom.: 16116 Cov.: 29

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.786

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.430

GnomAD4 exome AF: 0.508 AC: 230964 AN: 454984 Hom.: 61675 AF XY: 0.506 AC XY: 129232 AN XY: 255456

African (AFR) AF: 0.252 AC: 3298 AN: 13068

American (AMR) AF: 0.672 AC: 25359 AN: 37714

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 7602 AN: 14854

East Asian (EAS) AF: 0.781 AC: 17169 AN: 21994

South Asian (SAS) AF: 0.556 AC: 37344 AN: 67174

European-Finnish (FIN) AF: 0.565 AC: 13621 AN: 24104

Middle Eastern (MID) AF: 0.362 AC: 601 AN: 1662

European-Non Finnish (NFE) AF: 0.457 AC: 115123 AN: 251988

Other (OTH) AF: 0.484 AC: 10847 AN: 22426

GnomAD4 genome AF: 0.440 AC: 66666 AN: 151594 Hom.: 16130 Cov.: 29 AF XY: 0.455 AC XY: 33670 AN XY: 74032

African (AFR) AF: 0.253 AC: 10440 AN: 41314

American (AMR) AF: 0.572 AC: 8704 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1761 AN: 3468

East Asian (EAS) AF: 0.787 AC: 4010 AN: 5098

South Asian (SAS) AF: 0.602 AC: 2887 AN: 4796

European-Finnish (FIN) AF: 0.589 AC: 6182 AN: 10504

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31149 AN: 67892

Other (OTH) AF: 0.434 AC: 910 AN: 2098

Alfa AF: 0.388 Hom.: 1774

Bravo AF: 0.432

Asia WGS AF: 0.687 AC: 2385 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.9
DANN	Benign	0.43
PhyloP100		-2.2

Splicing

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

Other links and lift over

dbSNP: rs10446758; hg19: chr4-149447585;