4-74556244-A-G

Variant names:

• chr4-74556244-A-G
• rs9996584
• ENST00000510419.1:n.374-144T>C

Variant summary

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

The ENST00000510419.1(ENSG00000249942):​n.374-144T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 152,066 control chromosomes in the GnomAD database, including 29,084 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 0.60 (29084 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000249942 ENST00000510419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380
• Publications: 4 publications found

Genes affected

ENSG00000249942 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000510419.1. 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
	ENSG00000249942	ENST00000510419.1	TSL:5	n.374-144T>C		intron	N/A
	ENSG00000249942	ENST00000840127.1		n.419-3412T>C		intron	N/A
	ENSG00000249942	ENST00000840128.1		n.311-3412T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91235 AN: 151948 Hom.: 29070 Cov.: 32

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.581

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.600 AC: 91281 AN: 152066 Hom.: 29084 Cov.: 32 AF XY: 0.613 AC XY: 45562 AN XY: 74342

African (AFR) AF: 0.394 AC: 16341 AN: 41486

American (AMR) AF: 0.699 AC: 10666 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1873 AN: 3466

East Asian (EAS) AF: 0.987 AC: 5121 AN: 5186

South Asian (SAS) AF: 0.747 AC: 3601 AN: 4818

European-Finnish (FIN) AF: 0.748 AC: 7907 AN: 10568

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.646 AC: 43915 AN: 67964

Other (OTH) AF: 0.586 AC: 1237 AN: 2112

Alfa AF: 0.629 Hom.: 50428

Bravo AF: 0.587

Asia WGS AF: 0.843 AC: 2932 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.2
DANN	Benign	0.48
PhyloP100		0.038

Splicing

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

Other links and lift over

dbSNP: rs9996584; hg19: chr4-75421961;