4-124668002-C-T

Variant names:

• chr4-124668002-C-T
• rs1495127
• NM_020337.3:c.*4-488G>A

Variant summary

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

The NM_020337.3(ANKRD50):​c.*4-488G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 151,650 control chromosomes in the GnomAD database, including 4,401 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 0.23 (4401 hom., cov: 32)
• Consequence: ANKRD50 NM_020337.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129
• Publications: 1 publications found

Genes affected

ANKRD50 (HGNC:29223): (ankyrin repeat domain containing 50) Involved in endocytic recycling. Predicted to be located in endosome. [provided by Alliance of Genome Resources, Apr 2022]

ANKRD50 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD50	NM_020337.3	c.*4-488G>A		intron_variant	Intron 4 of 4	ENST00000504087.6	NP_065070.1
ANKRD50	NM_001167882.2	c.*4-488G>A		intron_variant	Intron 3 of 3		NP_001161354.1
ANKRD50	XM_017008471.2	c.*4-488G>A		intron_variant	Intron 3 of 3		XP_016863960.1
ANKRD50	XM_047415992.1	c.*4-488G>A		intron_variant	Intron 4 of 4		XP_047271948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD50	ENST00000504087.6	c.*4-488G>A		intron_variant	Intron 4 of 4	2	NM_020337.3	ENSP00000425658.1
ANKRD50	ENST00000515641.1	c.*4-488G>A		intron_variant	Intron 3 of 3	2		ENSP00000425355.1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35493 AN: 151532 Hom.: 4404 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.206

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.234 AC: 35506 AN: 151650 Hom.: 4401 Cov.: 32 AF XY: 0.236 AC XY: 17481 AN XY: 74126

African (AFR) AF: 0.323 AC: 13351 AN: 41350

American (AMR) AF: 0.212 AC: 3227 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 675 AN: 3468

East Asian (EAS) AF: 0.254 AC: 1306 AN: 5134

South Asian (SAS) AF: 0.276 AC: 1328 AN: 4818

European-Finnish (FIN) AF: 0.239 AC: 2519 AN: 10524

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12539 AN: 67836

Other (OTH) AF: 0.203 AC: 429 AN: 2114

Alfa AF: 0.214 Hom.: 563

Bravo AF: 0.236

Asia WGS AF: 0.243 AC: 839 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.9
DANN	Benign	0.19
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1495127; hg19: chr4-125589157;