rs1368114

Positions:

• chr2-38572678-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138394.4(HNRNPLL):​c.1092+532C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 151,926 control chromosomes in the GnomAD database, including 5,404 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 (5404 hom., cov: 32)
• Consequence: HNRNPLL NM_138394.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

Genes affected

HNRNPLL (HGNC:25127): (heterogeneous nuclear ribonucleoprotein L like) HNRNPLL is a master regulator of activation-induced alternative splicing in T cells. In particular, it alters splicing of CD45 (PTPRC; MIM 151460), a tyrosine phosphatase essential for T-cell development and activation (Oberdoerffer et al., 2008 [PubMed 18669861]).[supplied by OMIM, Aug 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNRNPLL	NM_138394.4	c.1092+532C>T		intron_variant		ENST00000449105.8	NP_612403.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNRNPLL	ENST00000449105.8	c.1092+532C>T		intron_variant		1	NM_138394.4	ENSP00000390625.3
HNRNPLL	ENST00000409636.5	c.1077+532C>T		intron_variant		2		ENSP00000387088.1
HNRNPLL	ENST00000409328.5	c.990+532C>T		intron_variant		1		ENSP00000386575.1
HNRNPLL	ENST00000272249.7	n.*326+532C>T		intron_variant		2		ENSP00000272249.3

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35581 AN: 151808 Hom.: 5376 Cov.: 32

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.0958

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.235 AC: 35642 AN: 151926 Hom.: 5404 Cov.: 32 AF XY: 0.230 AC XY: 17096 AN XY: 74276

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.0958

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.192

Alfa AF: 0.170 Hom.: 3066

Bravo AF: 0.249

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.60
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs1368114; hg19: chr2-38799820;