rs141885504

chr7-26193672-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_002137.4(HNRNPA2B1):c.744C>T(p.Pro248=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000351 in 1,611,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00031 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00035 (0 hom.)
• Consequence: HNRNPA2B1 NM_002137.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.06

Genes affected

HNRNPA2B1 (HGNC:5033): (heterogeneous nuclear ribonucleoprotein A2/B1) This gene belongs to the A/B subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene has two repeats of quasi-RRM domains that bind to RNAs. This gene has been described to generate two alternatively spliced transcript variants which encode different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.058010817).
• BP6: Variant 7-26193672-G-A is Benign according to our data. Variant chr7-26193672-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 474503.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-26193672-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=2.06 with no splicing effect.
• BS2: High AC in GnomAd at 47 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNRNPA2B1	NM_002137.4	c.744C>T	p.Pro248=	synonymous_variant	8/11	ENST00000618183.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNRNPA2B1	ENST00000618183.5	c.744C>T	p.Pro248=	synonymous_variant	8/11	5	NM_002137.4	A1

Frequencies

GnomAD3 genomes AF: 0.000309 AC: 47 AN: 151944 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000284

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000471

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000358 AC: 89 AN: 248678 Hom.: 0 AF XY: 0.000372 AC XY: 50 AN XY: 134536

Gnomad AFR exome AF: 0.000248

Gnomad AMR exome AF: 0.0000594

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000166

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000555

Gnomad NFE exome AF: 0.000593

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000355 AC: 518 AN: 1459282 Hom.: 0 Cov.: 30 AF XY: 0.000339 AC XY: 246 AN XY: 726032

Gnomad4 AFR exome AF: 0.000210

Gnomad4 AMR exome AF: 0.000113

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000506

Gnomad4 NFE exome AF: 0.000406

Gnomad4 OTH exome AF: 0.000332

GnomAD4 genome AF: 0.000309 AC: 47 AN: 151944 Hom.: 0 Cov.: 32 AF XY: 0.000283 AC XY: 21 AN XY: 74186

Gnomad4 AFR AF: 0.000242

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000284

Gnomad4 NFE AF: 0.000471

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000445 Hom.: 0

Bravo AF: 0.000351

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.000371 AC: 45

EpiCase AF: 0.000437

EpiControl AF: 0.000298

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 08, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.45
Cadd	Benign	15
Dann	Benign	0.32
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.49	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D
Sift4G	Uncertain	0.039	D
Vest4		0.21
MVP		0.64
ClinPred		0.086	T
GERP RS		3.7
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8

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: rs141885504; hg19: chr7-26233292;