rs12241995

Variant names:

• chr10-113597319-G-A
• rs12241995
• NM_198060.4:c.4333-135C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-113597319-G-A
• chr10-113597319-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_198060.4(NRAP):​c.4333-135C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 635,982 control chromosomes in the GnomAD database, including 22,360 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5097 hom., cov: 32)
  • Exomes 𝑓: 0.26 (17263 hom.)
• Consequence: NRAP NM_198060.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.278
• Publications: 2 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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 10-113597319-G-A is Benign according to our data. Variant chr10-113597319-G-A is described in ClinVar as Benign. ClinVar VariationId is 1294904.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRAP	NM_198060.4	c.4333-135C>T		intron_variant	Intron 36 of 41	ENST00000359988.4	NP_932326.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRAP	ENST00000359988.4	c.4333-135C>T		intron_variant	Intron 36 of 41	1	NM_198060.4	ENSP00000353078.3
NRAP	ENST00000369358.8	c.4333-135C>T		intron_variant	Intron 36 of 41	1		ENSP00000358365.4
NRAP	ENST00000360478.7	c.4228-135C>T		intron_variant	Intron 35 of 40	1		ENSP00000353666.3
NRAP	ENST00000369360.7	c.4252-135C>T		intron_variant	Intron 35 of 40	5		ENSP00000358367.3

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38455 AN: 151832 Hom.: 5087 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.277

GnomAD4 exome AF: 0.259 AC: 125343 AN: 484032 Hom.: 17263 AF XY: 0.260 AC XY: 67306 AN XY: 259148

African (AFR) AF: 0.263 AC: 3655 AN: 13890

American (AMR) AF: 0.295 AC: 7554 AN: 25644

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 2443 AN: 14350

East Asian (EAS) AF: 0.421 AC: 13294 AN: 31610

South Asian (SAS) AF: 0.298 AC: 15016 AN: 50450

European-Finnish (FIN) AF: 0.216 AC: 7826 AN: 36264

Middle Eastern (MID) AF: 0.265 AC: 939 AN: 3542

European-Non Finnish (NFE) AF: 0.241 AC: 67712 AN: 281440

Other (OTH) AF: 0.257 AC: 6904 AN: 26842

GnomAD4 genome AF: 0.253 AC: 38481 AN: 151950 Hom.: 5097 Cov.: 32 AF XY: 0.254 AC XY: 18828 AN XY: 74268

African (AFR) AF: 0.258 AC: 10682 AN: 41406

American (AMR) AF: 0.253 AC: 3864 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 567 AN: 3470

East Asian (EAS) AF: 0.429 AC: 2210 AN: 5150

South Asian (SAS) AF: 0.307 AC: 1475 AN: 4808

European-Finnish (FIN) AF: 0.222 AC: 2341 AN: 10554

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16395 AN: 67982

Other (OTH) AF: 0.277 AC: 584 AN: 2106

Alfa AF: 0.186 Hom.: 523

Bravo AF: 0.259

Asia WGS AF: 0.337 AC: 1170 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.7
DANN	Benign	0.17
PhyloP100		0.28
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: rs12241995; hg19: chr10-115357078; COSMIC: COSV63489223;