9-83969454-GAAAAA-GAAAA

Variant names:

• chr9-83969454-GA-G
• rs749772524
• NM_031263.4:c.1362-15delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_031263.4(HNRNPK):​c.1362-15delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,548,034 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00013 (1 hom.)
• Consequence: HNRNPK NM_031263.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.19
• Publications: 0 publications found

Genes affected

HNRNPK (HGNC:5044): (heterogeneous nuclear ribonucleoprotein K) This gene belongs to the 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 is located in the nucleoplasm and has three repeats of KH domains that binds to RNAs. It is distinct among other hnRNP proteins in its binding preference; it binds tenaciously to poly(C). This protein is also thought to have a role during cell cycle progession. Several alternatively spliced transcript variants have been described for this gene, however, not all of them are fully characterized. [provided by RefSeq, Jul 2008]

HNRNPK-AS1 (HGNC:56061): (HNRNPK antisense RNA 1)

ACMG classification

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

• BP6: Variant 9-83969454-GA-G is Benign according to our data. Variant chr9-83969454-GA-G is described in ClinVar as Benign. ClinVar VariationId is 1974011.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000125 (19/151588) while in subpopulation SAS AF = 0.000208 (1/4806). AF 95% confidence interval is 0.0000792. There are 0 homozygotes in GnomAd4. There are 12 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 19 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031263.4. 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
	HNRNPK	NM_031263.4	MANE Select	c.1362-15delT		intron	N/A	NP_112553.1	P61978-2
	HNRNPK	NM_002140.5		c.1362-15delT		intron	N/A	NP_002131.2
	HNRNPK	NM_001318188.2		c.1362-75delT		intron	N/A	NP_001305117.1	P61978-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPK	ENST00000376263.8	TSL:1 MANE Select	c.1362-15delT		intron	N/A	ENSP00000365439.3	P61978-2
	HNRNPK	ENST00000376281.8	TSL:1	c.1362-15delT		intron	N/A	ENSP00000365458.4	P61978-2
	HNRNPK	ENST00000360384.9	TSL:1	c.1362-75delT		intron	N/A	ENSP00000353552.5	P61978-1

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 151588 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000170

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.000287

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000884

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000168 AC: 36 AN: 214284 AF XY: 0.000170

Gnomad AFR exome AF: 0.000288

Gnomad AMR exome AF: 0.0000387

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000184

Gnomad FIN exome AF: 0.000336

Gnomad NFE exome AF: 0.000151

Gnomad OTH exome AF: 0.000198

GnomAD4 exome AF: 0.000125 AC: 175 AN: 1396446 Hom.: 1 Cov.: 26 AF XY: 0.000116 AC XY: 81 AN XY: 696980

African (AFR) AF: 0.000131 AC: 4 AN: 30612

American (AMR) AF: 0.000111 AC: 4 AN: 35970

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24544

East Asian (EAS) AF: 0.000152 AC: 6 AN: 39356

South Asian (SAS) AF: 0.000188 AC: 15 AN: 79806

European-Finnish (FIN) AF: 0.000267 AC: 14 AN: 52472

Middle Eastern (MID) AF: 0.000361 AC: 2 AN: 5544

European-Non Finnish (NFE) AF: 0.000113 AC: 121 AN: 1070254

Other (OTH) AF: 0.000155 AC: 9 AN: 57888

GnomAD4 genome AF: 0.000125 AC: 19 AN: 151588 Hom.: 0 Cov.: 33 AF XY: 0.000162 AC XY: 12 AN XY: 73988

African (AFR) AF: 0.000170 AC: 7 AN: 41262

American (AMR) AF: 0.0000656 AC: 1 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4806

European-Finnish (FIN) AF: 0.000287 AC: 3 AN: 10454

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000884 AC: 6 AN: 67862

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000982

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs749772524; hg19: chr9-86584369; COSMIC: COSV61088253; COSMIC: COSV61088253;