5-136180020-A-G

Position:

• chr5-136180020-A-G

Variant summary

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

The ENST00000545279.6(SMAD5):​c.*2540A>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 152,076 control chromosomes in the GnomAD database, including 10,557 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 (10557 hom., cov: 33)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: SMAD5 ENST00000545279.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.420

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=-0.84).
• 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	Protein	UniProt
SMAD5	NM_005903.7	c.*2540A>G		3_prime_UTR_variant	8/8	ENST00000545279.6	NP_005894.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMAD5	ENST00000545279.6	c.*2540A>G		3_prime_UTR_variant	8/8	1	NM_005903.7	ENSP00000441954	P1
SMAD5	ENST00000545620.5	c.*2540A>G		3_prime_UTR_variant	7/7	5		ENSP00000446474	P1
SMAD5	ENST00000513418.1	c.164+5388A>G		intron_variant, NMD_transcript_variant		5		ENSP00000427650

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54190 AN: 151958 Hom.: 10529 Cov.: 33

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.375

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: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.357 AC: 54262 AN: 152074 Hom.: 10557 Cov.: 33 AF XY: 0.352 AC XY: 26203 AN XY: 74352

Gnomad4 AFR AF: 0.527

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.375

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.385

Alfa AF: 0.313 Hom.: 7287

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	-0.84
CADD	Benign	1.2
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs6865297; hg19: chr5-135515708;