10-43408759-A-G

Variant names:

• chr10-43408759-A-G
• rs1416226
• NM_001098204.2:c.-247+372T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001098204.2(HNRNPF):​c.-247+372T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 152,014 control chromosomes in the GnomAD database, including 34,294 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 0.65 (34282 hom., cov: 32)
  • Exomes 𝑓: 0.67 (12 hom.)
• Consequence: HNRNPF NM_001098204.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.80
• Publications: 6 publications found

Genes affected

HNRNPF (HGNC:5039): (heterogeneous nuclear ribonucleoprotein F) This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins that complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and regulate alternative splicing, polyadenylation, 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 three repeats of quasi-RRM domains that bind to RNAs which have guanosine-rich sequences. This protein is very similar to the family member hnRPH. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

LINC02916 (HGNC:55574): (long intergenic non-protein coding RNA 2916)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNRNPF	NM_001098204.2	c.-247+372T>C		intron_variant	Intron 1 of 3	ENST00000682386.1	NP_001091674.1
HNRNPF	NM_001098205.2	c.-279T>C		5_prime_UTR_variant	Exon 1 of 4		NP_001091675.1
HNRNPF	NM_004966.4	c.-247+331T>C		intron_variant	Intron 1 of 3		NP_004957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNRNPF	ENST00000682386.1	c.-247+372T>C		intron_variant	Intron 1 of 3		NM_001098204.2	ENSP00000507787.1
HNRNPF	ENST00000337970.7	c.-247+331T>C		intron_variant	Intron 1 of 3	1		ENSP00000338477.3
HNRNPF	ENST00000356053.7	c.-279T>C		5_prime_UTR_variant	Exon 1 of 4	2		ENSP00000348345.3
LINC02916	ENST00000745706.1	n.68+842A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99455 AN: 151844 Hom.: 34273 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.765

Gnomad OTH AF: 0.692

GnomAD4 exome AF: 0.673 AC: 35 AN: 52 Hom.: 12 Cov.: 0 AF XY: 0.636 AC XY: 28 AN XY: 44

African (AFR) AC: 0 AN: 0

American (AMR) AF: 1.00 AC: 2 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.875 AC: 7 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.625 AC: 25 AN: 40

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.655 AC: 99497 AN: 151962 Hom.: 34282 Cov.: 32 AF XY: 0.654 AC XY: 48603 AN XY: 74286

African (AFR) AF: 0.415 AC: 17216 AN: 41448

American (AMR) AF: 0.715 AC: 10920 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2238 AN: 3472

East Asian (EAS) AF: 0.734 AC: 3746 AN: 5104

South Asian (SAS) AF: 0.643 AC: 3096 AN: 4812

European-Finnish (FIN) AF: 0.749 AC: 7931 AN: 10582

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.765 AC: 51985 AN: 67950

Other (OTH) AF: 0.693 AC: 1464 AN: 2112

Alfa AF: 0.709 Hom.: 12659

Bravo AF: 0.643

Asia WGS AF: 0.670 AC: 2332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.72
PhyloP100		1.8
PromoterAI		0.031	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1416226; hg19: chr10-43904207;