NM_005903.7:c.-245+2383T>C

Variant names:

• chr5-136135345-T-C
• rs7356756
• NM_005903.7:c.-245+2383T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005903.7(SMAD5):​c.-245+2383T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 152,098 control chromosomes in the GnomAD database, including 10,860 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (10860 hom., cov: 32)
• Consequence: SMAD5 NM_005903.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326
• Publications: 7 publications found

Genes affected

SMAD5 (HGNC:6771): (SMAD family member 5) The protein encoded by this gene is involved in the transforming growth factor beta signaling pathway that results in an inhibition of the proliferation of hematopoietic progenitor cells. The encoded protein is activated by bone morphogenetic proteins type 1 receptor kinase, and may be involved in cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005903.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMAD5	NM_005903.7	MANE Select	c.-245+2383T>C		intron	N/A	NP_005894.3
	SMAD5	NM_001001419.3		c.-329+2383T>C		intron	N/A	NP_001001419.1
	SMAD5	NM_001001420.3		c.-170+2383T>C		intron	N/A	NP_001001420.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMAD5	ENST00000545279.6	TSL:1 MANE Select	c.-245+2383T>C		intron	N/A	ENSP00000441954.2
	SMAD5	ENST00000509297.6	TSL:1	c.-245+1386T>C		intron	N/A	ENSP00000426696.2
	SMAD5	ENST00000511116.5	TSL:1	c.-329+2383T>C		intron	N/A	ENSP00000424279.1

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54719 AN: 151980 Hom.: 10831 Cov.: 32

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.383

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.360 AC: 54794 AN: 152098 Hom.: 10860 Cov.: 32 AF XY: 0.356 AC XY: 26457 AN XY: 74350

African (AFR) AF: 0.539 AC: 22337 AN: 41468

American (AMR) AF: 0.284 AC: 4337 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1187 AN: 3468

East Asian (EAS) AF: 0.377 AC: 1950 AN: 5178

South Asian (SAS) AF: 0.187 AC: 903 AN: 4826

European-Finnish (FIN) AF: 0.301 AC: 3184 AN: 10584

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19810 AN: 67980

Other (OTH) AF: 0.385 AC: 812 AN: 2110

Alfa AF: 0.334 Hom.: 1560

Bravo AF: 0.374

Asia WGS AF: 0.343 AC: 1197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	20
DANN	Benign	0.80
PhyloP100		0.33
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: rs7356756; hg19: chr5-135471034;