5-136180515-T-C

Variant names:

• chr5-136180515-T-C
• rs3206634
• NM_005903.7:c.*3035T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005903.7(SMAD5):​c.*3035T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 151,802 control chromosomes in the GnomAD database, including 10,484 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 (10484 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SMAD5 NM_005903.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71
• Publications: 17 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.52 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.*3035T>C		3_prime_UTR	Exon 8 of 8	NP_005894.3
	SMAD5	NM_001001419.3		c.*3035T>C		3_prime_UTR	Exon 9 of 9	NP_001001419.1
	SMAD5	NM_001001420.3		c.*3035T>C		3_prime_UTR	Exon 7 of 7	NP_001001420.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMAD5	ENST00000545279.6	TSL:1 MANE Select	c.*3035T>C		3_prime_UTR	Exon 8 of 8	ENSP00000441954.2
	SMAD5	ENST00000545620.5	TSL:5	c.*3035T>C		3_prime_UTR	Exon 7 of 7	ENSP00000446474.2
	SMAD5	ENST00000513418.1	TSL:5	n.162+5883T>C		intron	N/A	ENSP00000427650.1

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54016 AN: 151684 Hom.: 10456 Cov.: 32

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.382

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.356 AC: 54089 AN: 151802 Hom.: 10484 Cov.: 32 AF XY: 0.352 AC XY: 26100 AN XY: 74180

African (AFR) AF: 0.526 AC: 21768 AN: 41368

American (AMR) AF: 0.281 AC: 4296 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1184 AN: 3458

East Asian (EAS) AF: 0.375 AC: 1941 AN: 5176

South Asian (SAS) AF: 0.185 AC: 891 AN: 4822

European-Finnish (FIN) AF: 0.300 AC: 3167 AN: 10550

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

European-Non Finnish (NFE) AF: 0.291 AC: 19761 AN: 67856

Other (OTH) AF: 0.384 AC: 807 AN: 2104

Alfa AF: 0.328 Hom.: 7749

Bravo AF: 0.370

Asia WGS AF: 0.341 AC: 1188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.18
DANN	Benign	0.44
PhyloP100		-1.7
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: rs3206634; hg19: chr5-135516203;