rs6865297

Variant names:

• chr5-136180020-A-G
• rs6865297
• NM_005903.7:c.*2540A>G

Variant summary

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

The NM_005903.7(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 NM_005903.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.420
• Publications: 12 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=-0.84).
• 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 rank	MANE	Protein	UniProt
SMAD5	NM_005903.7	c.*2540A>G		3_prime_UTR_variant	Exon 8 of 8	ENST00000545279.6	NP_005894.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMAD5	ENST00000545279.6	c.*2540A>G		3_prime_UTR_variant	Exon 8 of 8	1	NM_005903.7	ENSP00000441954.2
SMAD5	ENST00000545620.5	c.*2540A>G		3_prime_UTR_variant	Exon 7 of 7	5		ENSP00000446474.2
SMAD5	ENST00000513418.1	n.162+5388A>G		intron_variant	Intron 1 of 2	5		ENSP00000427650.1

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

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) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.527 AC: 21831 AN: 41462

American (AMR) AF: 0.282 AC: 4315 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1187 AN: 3466

East Asian (EAS) AF: 0.375 AC: 1939 AN: 5166

South Asian (SAS) AF: 0.185 AC: 894 AN: 4830

European-Finnish (FIN) AF: 0.302 AC: 3192 AN: 10586

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

European-Non Finnish (NFE) AF: 0.292 AC: 19816 AN: 67948

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

Alfa AF: 0.316 Hom.: 9170

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
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6865297; hg19: chr5-135515708;