10-113588967-GA-G

Variant names:

• chr10-113588967-GA-G
• rs3832698
• NM_198060.4:c.*7delT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_198060.4(NRAP):​c.*7delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (9912 hom., cov: 0)
  • Exomes 𝑓: 0.34 (86918 hom.)
• Consequence: NRAP NM_198060.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.529
• Publications: 1 publications found

Genes affected

NRAP (HGNC:7988): (nebulin related anchoring protein) Predicted to enable actin filament binding activity and muscle alpha-actinin binding activity. Predicted to be involved in cardiac muscle thin filament assembly. Predicted to be located in fascia adherens; muscle tendon junction; and myofibril. Predicted to be active in Z disc. [provided by Alliance of Genome Resources, Apr 2022]

HABP2 (HGNC:4798): (hyaluronan binding protein 2) This gene encodes a member of the peptidase S1 family of serine proteases. The encoded preproprotein is secreted by hepatocytes and proteolytically processed to generate heavy and light chains that form the mature heterodimer. Further autoproteolysis leads to smaller, inactive peptides. This extracellular protease binds hyaluronic acid and may play a role in the coagulation and fibrinolysis systems. Mutations in this gene are associated with nonmedullary thyroid cancer and susceptibility to venous thromboembolism. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 10-113588967-GA-G is Benign according to our data. Variant chr10-113588967-GA-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 298930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198060.4. 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
	NRAP	NM_198060.4	MANE Select	c.*7delT		3_prime_UTR	Exon 42 of 42	NP_932326.2
	HABP2	NM_004132.5	MANE Select	c.*599delA		3_prime_UTR	Exon 13 of 13	NP_004123.1	Q14520-1
	NRAP	NM_001261463.2		c.*7delT		3_prime_UTR	Exon 42 of 42	NP_001248392.1	A0A0A0MRM2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRAP	ENST00000359988.4	TSL:1 MANE Select	c.*7delT		3_prime_UTR	Exon 42 of 42	ENSP00000353078.3	Q86VF7-1
	HABP2	ENST00000351270.4	TSL:1 MANE Select	c.*599delA		3_prime_UTR	Exon 13 of 13	ENSP00000277903.4	Q14520-1
	NRAP	ENST00000369358.8	TSL:1	c.*7delT		3_prime_UTR	Exon 42 of 42	ENSP00000358365.4	A0A0A0MRM2

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54360 AN: 151770 Hom.: 9898 Cov.: 0

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.354

GnomAD2 exomes AF: 0.355 AC: 88302 AN: 248872 AF XY: 0.348

Gnomad AFR exome AF: 0.371

Gnomad AMR exome AF: 0.493

Gnomad ASJ exome AF: 0.347

Gnomad EAS exome AF: 0.305

Gnomad FIN exome AF: 0.299

Gnomad NFE exome AF: 0.339

Gnomad OTH exome AF: 0.352

GnomAD4 exome AF: 0.343 AC: 499910 AN: 1455502 Hom.: 86918 Cov.: 0 AF XY: 0.342 AC XY: 247812 AN XY: 724572

African (AFR) AF: 0.377 AC: 12568 AN: 33350

American (AMR) AF: 0.484 AC: 21623 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 8995 AN: 26084

East Asian (EAS) AF: 0.313 AC: 12407 AN: 39648

South Asian (SAS) AF: 0.316 AC: 27228 AN: 86122

European-Finnish (FIN) AF: 0.301 AC: 16103 AN: 53414

Middle Eastern (MID) AF: 0.331 AC: 1901 AN: 5744

European-Non Finnish (NFE) AF: 0.342 AC: 378496 AN: 1106270

Other (OTH) AF: 0.342 AC: 20589 AN: 60182

GnomAD4 genome AF: 0.358 AC: 54415 AN: 151888 Hom.: 9912 Cov.: 0 AF XY: 0.356 AC XY: 26454 AN XY: 74248

African (AFR) AF: 0.377 AC: 15582 AN: 41382

American (AMR) AF: 0.457 AC: 6974 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1173 AN: 3462

East Asian (EAS) AF: 0.317 AC: 1639 AN: 5166

South Asian (SAS) AF: 0.315 AC: 1515 AN: 4806

European-Finnish (FIN) AF: 0.293 AC: 3100 AN: 10568

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23230 AN: 67924

Other (OTH) AF: 0.352 AC: 743 AN: 2110

Alfa AF: 0.256 Hom.: 885

Bravo AF: 0.370

Asia WGS AF: 0.320 AC: 1111 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Factor VII Marburg I Variant Thrombophilia (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.53
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: rs3832698; hg19: chr10-115348726;