16-14140747-C-T

Variant names:

• chr16-14140747-C-T
• rs79629931
• NM_001308142.2:c.141C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001308142.2(MRTFB):​c.141C>T​(p.Asn47Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00375 in 1,613,960 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0025 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0039 (12 hom.)
• Consequence: MRTFB NM_001308142.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.96
• Publications: 1 publications found

Genes affected

MRTFB (HGNC:29819): (myocardin related transcription factor B) Enables transcription coactivator activity. Involved in positive regulation of pri-miRNA transcription by RNA polymerase II and positive regulation of striated muscle tissue development. Predicted to be located in cytoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MRTFB Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 16-14140747-C-T is Benign according to our data. Variant chr16-14140747-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 710820.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.96 with no splicing effect.
• BS2: High AC in GnomAd4 at 381 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308142.2. 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
	MRTFB	NM_001308142.2	MANE Select	c.141C>T	p.Asn47Asn	synonymous	Exon 3 of 17	NP_001295071.1	Q9ULH7-5
	MRTFB	NM_001365412.2		c.141C>T	p.Asn47Asn	synonymous	Exon 4 of 17	NP_001352341.1
	MRTFB	NM_014048.4		c.141C>T	p.Asn47Asn	synonymous	Exon 3 of 17	NP_054767.3	Q9ULH7-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRTFB	ENST00000571589.6	TSL:2 MANE Select	c.141C>T	p.Asn47Asn	synonymous	Exon 3 of 17	ENSP00000459626.2	Q9ULH7-5
	MRTFB	ENST00000574045.5	TSL:1	c.141C>T	p.Asn47Asn	synonymous	Exon 3 of 17	ENSP00000459205.1	Q9ULH7-4
	MRTFB	ENST00000910537.1		c.141C>T	p.Asn47Asn	synonymous	Exon 3 of 17	ENSP00000580596.1

Frequencies

GnomAD3 genomes AF: 0.00251 AC: 381 AN: 152008 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000725

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00498

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.000284

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00385

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00224 AC: 563 AN: 251370 AF XY: 0.00220

Gnomad AFR exome AF: 0.000615

Gnomad AMR exome AF: 0.00173

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.000370

Gnomad NFE exome AF: 0.00400

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00388 AC: 5671 AN: 1461834 Hom.: 12 Cov.: 30 AF XY: 0.00374 AC XY: 2722 AN XY: 727216

African (AFR) AF: 0.000329 AC: 11 AN: 33480

American (AMR) AF: 0.00273 AC: 122 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26132

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39694

South Asian (SAS) AF: 0.000591 AC: 51 AN: 86256

European-Finnish (FIN) AF: 0.000580 AC: 31 AN: 53418

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.00468 AC: 5206 AN: 1111976

Other (OTH) AF: 0.00401 AC: 242 AN: 60390

GnomAD4 genome AF: 0.00250 AC: 381 AN: 152126 Hom.: 1 Cov.: 32 AF XY: 0.00227 AC XY: 169 AN XY: 74358

African (AFR) AF: 0.000723 AC: 30 AN: 41514

American (AMR) AF: 0.00491 AC: 75 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5158

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4822

European-Finnish (FIN) AF: 0.000284 AC: 3 AN: 10558

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00387 AC: 263 AN: 68008

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00330 Hom.: 0

Bravo AF: 0.00297

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00458

EpiControl AF: 0.00385

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	6.3
DANN	Benign	0.74
PhyloP100		-3.0
PromoterAI		-0.047	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs79629931; hg19: chr16-14234604; COSMIC: COSV105895491;