rs7031

Variant names:

• chr5-136182554-G-A
• rs7031
• NM_005903.7:c.*5074G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-136182554-G-A
• chr5-136182554-G-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_005903.7(SMAD5):​c.*5074G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000395 in 152,084 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000039 (0 hom., cov: 33)
• Consequence: SMAD5 NM_005903.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.560
• Publications: 13 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BS2: High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMAD5	NM_005903.7	c.*5074G>A		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.*5074G>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_005903.7	ENSP00000441954.2
SMAD5	ENST00000545620.5	c.*5074G>A		3_prime_UTR_variant	Exon 7 of 7	5		ENSP00000446474.2
SMAD5	ENST00000513418.1	n.163-4607G>A		intron_variant	Intron 1 of 2	5		ENSP00000427650.1

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 151966 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000589

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000395 AC: 6 AN: 152084 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74352

African (AFR) AF: 0.0000482 AC: 2 AN: 41488

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10550

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000589 AC: 4 AN: 67960

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 2411

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	12
DANN	Benign	0.82
PhyloP100		0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs7031; hg19: chr5-135518242;