chr10-110644604-A-T

Variant names:

• chr10-110644604-A-T
• rs376936285
• NM_001134363.3:c.150A>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001134363.3(RBM20):​c.150A>T​(p.Pro50Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000462 in 1,144,878 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P50P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0021 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00023 (1 hom.)
• Consequence: RBM20 NM_001134363.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:14
• Conservation: PhyloP100: -1.80
• Publications: 1 publications found

Genes affected

RBM20 (HGNC:27424): (RNA binding motif protein 20) This gene encodes a protein that binds RNA and regulates splicing. Mutations in this gene have been associated with familial dilated cardiomyopathy. [provided by RefSeq, Apr 2014]

RBM20 Gene-Disease associations (from GenCC):

• dilated cardiomyopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• dilated cardiomyopathy 1DD

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 10-110644604-A-T is Benign according to our data. Variant chr10-110644604-A-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 43974.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.8 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00211 (293/138606) while in subpopulation AFR AF = 0.00753 (286/38006). AF 95% confidence interval is 0.00681. There are 1 homozygotes in GnomAd4. There are 137 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 293 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134363.3. 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
	RBM20	NM_001134363.3	MANE Select	c.150A>T	p.Pro50Pro	synonymous	Exon 1 of 14	NP_001127835.2	Q5T481

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM20	ENST00000369519.4	TSL:1 MANE Select	c.150A>T	p.Pro50Pro	synonymous	Exon 1 of 14	ENSP00000358532.3	Q5T481
	RBM20	ENST00000961386.1		c.150A>T	p.Pro50Pro	synonymous	Exon 1 of 14	ENSP00000631445.1
	RBM20	ENST00000718239.1		c.150A>T	p.Pro50Pro	synonymous	Exon 1 of 14	ENSP00000520684.1	Q5T481

Frequencies

GnomAD3 genomes AF: 0.00205 AC: 284 AN: 138454 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00731

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000282

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00155

GnomAD2 exomes AF: 0.000262 AC: 30 AN: 114532 AF XY: 0.000141

Gnomad AFR exome AF: 0.00696

Gnomad AMR exome AF: 0.000375

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000235 AC: 236 AN: 1006272 Hom.: 1 Cov.: 35 AF XY: 0.000185 AC XY: 93 AN XY: 502360

African (AFR) AF: 0.00912 AC: 186 AN: 20394

American (AMR) AF: 0.000321 AC: 9 AN: 28014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16668

East Asian (EAS) AF: 0.00 AC: 0 AN: 18154

South Asian (SAS) AF: 0.00 AC: 0 AN: 71322

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25134

Middle Eastern (MID) AF: 0.000327 AC: 1 AN: 3062

European-Non Finnish (NFE) AF: 0.00000255 AC: 2 AN: 784278

Other (OTH) AF: 0.000968 AC: 38 AN: 39246

GnomAD4 genome AF: 0.00211 AC: 293 AN: 138606 Hom.: 1 Cov.: 32 AF XY: 0.00203 AC XY: 137 AN XY: 67370

African (AFR) AF: 0.00753 AC: 286 AN: 38006

American (AMR) AF: 0.000282 AC: 4 AN: 14196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3288

East Asian (EAS) AF: 0.00 AC: 0 AN: 3876

South Asian (SAS) AF: 0.00 AC: 0 AN: 3736

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8748

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 246

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 63720

Other (OTH) AF: 0.00153 AC: 3 AN: 1960

Alfa AF: 0.0000436 Hom.: 0

Bravo AF: 0.00199

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	3	Dilated cardiomyopathy 1DD (3)
-	-	3	not provided (3)
-	-	1	Cardiomyopathy (1)
-	-	1	Cardiovascular phenotype (1)
-	-	1	Primary dilated cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.075
DANN	Benign	0.83
PhyloP100		-1.8
PromoterAI		-0.020	Neutral
Mutation Taster		=100/0	polymorphism

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: rs376936285; hg19: chr10-112404362;