rs12719481

Positions:

• chr5-136178367-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005903.7(SMAD5):​c.*887A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,514 control chromosomes in the GnomAD database, including 10,603 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 (10581 hom., cov: 33)
  • Exomes 𝑓: 0.32 (22 hom.)
• Consequence: SMAD5 NM_005903.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMAD5	NM_005903.7	c.*887A>G		3_prime_UTR_variant	8/8	ENST00000545279.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMAD5	ENST00000545279.6	c.*887A>G		3_prime_UTR_variant	8/8	1	NM_005903.7	P1
SMAD5	ENST00000545620.5	c.*887A>G		3_prime_UTR_variant	7/7	5		P1
SMAD5	ENST00000513418.1	c.164+3735A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54238 AN: 151966 Hom.: 10553 Cov.: 33

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.383

GnomAD4 exome AF: 0.316 AC: 136 AN: 430 Hom.: 22 Cov.: 0 AF XY: 0.341 AC XY: 88 AN XY: 258

Gnomad4 FIN exome AF: 0.318

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.357 AC: 54311 AN: 152084 Hom.: 10581 Cov.: 33 AF XY: 0.353 AC XY: 26242 AN XY: 74366

Gnomad4 AFR AF: 0.527

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.377

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.385

Alfa AF: 0.312 Hom.: 7449

Bravo AF: 0.370

Asia WGS AF: 0.341 AC: 1188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	14
DANN	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs12719481; hg19: chr5-135514055; COSMIC: COSV72597479; COSMIC: COSV72597479;