rs8548

Variant names:

• chr14-103733243-A-C
• rs8548
• NM_015316.3:c.*1911T>G

Your query was ambiguous. Multiple possible variants found:

• chr14-103733243-A-C
• chr14-103733243-A-G

Variant summary

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

The NM_015316.3(PPP1R13B):​c.*1911T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 574,164 control chromosomes in the GnomAD database, including 27,315 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 0.27 (6493 hom., cov: 33)
  • Exomes 𝑓: 0.30 (20822 hom.)
• Consequence: PPP1R13B NM_015316.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.589
• Publications: 17 publications found

Genes affected

PPP1R13B (HGNC:14950): (protein phosphatase 1 regulatory subunit 13B) This gene encodes a member of the ASPP (apoptosis-stimulating protein of p53) family of p53 interacting proteins. The protein contains four ankyrin repeats and an SH3 domain involved in protein-protein interactions. ASPP proteins are required for the induction of apoptosis by p53-family proteins. They promote DNA binding and transactivation of p53-family proteins on the promoters of proapoptotic genes. Expression of this gene is regulated by the E2F transcription factor. [provided by RefSeq, Jul 2008]

ZFYVE21 (HGNC:20760): (zinc finger FYVE-type containing 21) Predicted to enable metal ion binding activity. Predicted to be located in endosome and focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015316.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R13B	NM_015316.3	MANE Select	c.*1911T>G		3_prime_UTR	Exon 17 of 17	NP_056131.2	Q96KQ4
	ZFYVE21	NM_024071.4	MANE Select	c.*225A>C		3_prime_UTR	Exon 7 of 7	NP_076976.1	Q9BQ24-1
	ZFYVE21	NM_001198953.2		c.*225A>C		3_prime_UTR	Exon 8 of 8	NP_001185882.1	Q9BQ24-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R13B	ENST00000202556.14	TSL:1 MANE Select	c.*1911T>G		3_prime_UTR	Exon 17 of 17	ENSP00000202556.9	Q96KQ4
	ZFYVE21	ENST00000311141.7	TSL:1 MANE Select	c.*225A>C		3_prime_UTR	Exon 7 of 7	ENSP00000310543.2	Q9BQ24-1
	ZFYVE21	ENST00000555501.1	TSL:1	n.4032A>C		non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41144 AN: 151072 Hom.: 6482 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.195

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.259

GnomAD4 exome AF: 0.304 AC: 128650 AN: 422972 Hom.: 20822 Cov.: 5 AF XY: 0.299 AC XY: 66064 AN XY: 220922

African (AFR) AF: 0.112 AC: 1326 AN: 11828

American (AMR) AF: 0.265 AC: 4336 AN: 16384

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 2754 AN: 12714

East Asian (EAS) AF: 0.331 AC: 9292 AN: 28078

South Asian (SAS) AF: 0.201 AC: 7954 AN: 39496

European-Finnish (FIN) AF: 0.388 AC: 10539 AN: 27162

Middle Eastern (MID) AF: 0.198 AC: 426 AN: 2152

European-Non Finnish (NFE) AF: 0.326 AC: 85141 AN: 261084

Other (OTH) AF: 0.286 AC: 6882 AN: 24074

GnomAD4 genome AF: 0.272 AC: 41171 AN: 151192 Hom.: 6493 Cov.: 33 AF XY: 0.272 AC XY: 20117 AN XY: 73860

African (AFR) AF: 0.116 AC: 4759 AN: 40880

American (AMR) AF: 0.273 AC: 4168 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 780 AN: 3464

East Asian (EAS) AF: 0.329 AC: 1702 AN: 5176

South Asian (SAS) AF: 0.212 AC: 1015 AN: 4786

European-Finnish (FIN) AF: 0.412 AC: 4335 AN: 10530

Middle Eastern (MID) AF: 0.205 AC: 59 AN: 288

European-Non Finnish (NFE) AF: 0.347 AC: 23510 AN: 67808

Other (OTH) AF: 0.261 AC: 550 AN: 2108

Alfa AF: 0.314 Hom.: 5165

Bravo AF: 0.252

Asia WGS AF: 0.261 AC: 907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.2
DANN	Benign	0.79
PhyloP100		0.59
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: rs8548; hg19: chr14-104199580; COSMIC: COSV52448752; COSMIC: COSV52448752;