rs4213

Variant names:

• chr12-119681378-T-G
• rs4213
• ENST00000542698.1:n.3778T>G

Variant summary

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

The ENST00000542698.1(PRKAB1):​n.3778T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 152,076 control chromosomes in the GnomAD database, including 8,624 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 0.33 (8620 hom., cov: 32)
  • Exomes 𝑓: 0.26 (4 hom.)
• Consequence: PRKAB1 ENST00000542698.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.841
• Publications: 22 publications found

Genes affected

PRKAB1 (HGNC:9378): (protein kinase AMP-activated non-catalytic subunit beta 1) The protein encoded by this gene is a regulatory subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer consisting of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. AMPK is an important energy-sensing enzyme that monitors cellular energy status. In response to cellular metabolic stresses, AMPK is activated, and thus phosphorylates and inactivates acetyl-CoA carboxylase (ACC) and beta-hydroxy beta-methylglutaryl-CoA reductase (HMGCR), key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This subunit may be a positive regulator of AMPK activity. The myristoylation and phosphorylation of this subunit have been shown to affect the enzyme activity and cellular localization of AMPK. This subunit may also serve as an adaptor molecule mediating the association of the AMPK complex. [provided by RefSeq, Jul 2008]

LOC124903033 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKAB1	NM_006253.5	c.*1053T>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000229328.10	NP_006244.2
PRKAB1	XM_005253909.2	c.*1053T>G		3_prime_UTR_variant	Exon 8 of 8		XP_005253966.1
LOC124903033	XR_007063485.1	n.165+3944A>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKAB1	ENST00000542698.1	n.3778T>G		non_coding_transcript_exon_variant	Exon 2 of 2	1
PRKAB1	ENST00000229328.10	c.*1053T>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_006253.5	ENSP00000229328.5
PRKAB1	ENST00000541640.5	c.*1053T>G		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000441369.1
PRKAB1	ENST00000537057.1	n.1301T>G		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49395 AN: 151852 Hom.: 8613 Cov.: 32

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.0139

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.315

GnomAD4 exome AF: 0.259 AC: 28 AN: 108 Hom.: 4 Cov.: 0 AF XY: 0.241 AC XY: 13 AN XY: 54

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) AF: 0.293 AC: 27 AN: 92

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.100 AC: 1 AN: 10

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.325 AC: 49421 AN: 151968 Hom.: 8620 Cov.: 32 AF XY: 0.318 AC XY: 23586 AN XY: 74284

African (AFR) AF: 0.424 AC: 17571 AN: 41444

American (AMR) AF: 0.256 AC: 3909 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 986 AN: 3470

East Asian (EAS) AF: 0.0139 AC: 72 AN: 5162

South Asian (SAS) AF: 0.206 AC: 990 AN: 4806

European-Finnish (FIN) AF: 0.277 AC: 2925 AN: 10568

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.325 AC: 22063 AN: 67930

Other (OTH) AF: 0.311 AC: 655 AN: 2108

Alfa AF: 0.334 Hom.: 1565

Bravo AF: 0.326

Asia WGS AF: 0.136 AC: 477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.14
DANN	Benign	0.46
PhyloP100		-0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs4213; hg19: chr12-120119183;