rs148939821

Variant names:

• chr7-11406947-C-T
• rs148939821
• NM_015204.3:c.4025G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-11406947-C-T
• chr7-11406947-C-G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_015204.3(THSD7A):​c.4025G>A​(p.Arg1342Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000998 in 1,613,794 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0047 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00061 (4 hom.)
• Consequence: THSD7A NM_015204.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.162
• Publications: 2 publications found

Genes affected

THSD7A (HGNC:22207): (thrombospondin type 1 domain containing 7A) The protein encoded by this gene is found almost exclusively in endothelial cells from placenta and umbilical cord. The encoded protein appears to interact with alpha(V)beta(3) integrin and paxillin to inhibit endothelial cell migration and tube formation. This protein may be involved in cytoskeletal organization. Variations in this gene may be associated with low bone mineral density in osteoporosis. [provided by RefSeq, Aug 2010]

ENSG00000230333 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0054184496).
• BP6: Variant 7-11406947-C-T is Benign according to our data. Variant chr7-11406947-C-T is described in ClinVar as Benign. ClinVar VariationId is 781897.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 5 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015204.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THSD7A	NM_015204.3	MANE Select	c.4025G>A	p.Arg1342Gln	missense	Exon 21 of 28	NP_056019.1	Q9UPZ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THSD7A	ENST00000423059.9	TSL:5 MANE Select	c.4025G>A	p.Arg1342Gln	missense	Exon 21 of 28	ENSP00000406482.2	Q9UPZ6
	ENSG00000230333	ENST00000445839.5	TSL:4	n.441+23039C>T		intron	N/A
	ENSG00000230435	ENST00000425837.1	TSL:4	n.-8C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.00474 AC: 721 AN: 152114 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00807

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00142 AC: 353 AN: 248726 AF XY: 0.00106

Gnomad AFR exome AF: 0.0159

Gnomad AMR exome AF: 0.000814

Gnomad ASJ exome AF: 0.00538

Gnomad EAS exome AF: 0.000111

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000142

Gnomad OTH exome AF: 0.000993

GnomAD4 exome AF: 0.000608 AC: 889 AN: 1461562 Hom.: 4 Cov.: 31 AF XY: 0.000576 AC XY: 419 AN XY: 727054

African (AFR) AF: 0.0145 AC: 484 AN: 33472

American (AMR) AF: 0.000895 AC: 40 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00670 AC: 175 AN: 26126

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39694

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00173 AC: 10 AN: 5766

European-Non Finnish (NFE) AF: 0.0000549 AC: 61 AN: 1111808

Other (OTH) AF: 0.00176 AC: 106 AN: 60370

GnomAD4 genome AF: 0.00474 AC: 722 AN: 152232 Hom.: 5 Cov.: 32 AF XY: 0.00450 AC XY: 335 AN XY: 74442

African (AFR) AF: 0.0159 AC: 661 AN: 41536

American (AMR) AF: 0.00144 AC: 22 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00807 AC: 28 AN: 3470

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

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68006

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.00187 Hom.: 6

Bravo AF: 0.00518

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0122 AC: 48

ESP6500EA AF: 0.000721 AC: 6

ExAC AF: 0.00161 AC: 195

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	12
DANN	Benign	0.84
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.0054	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.16
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.066
Sift	Benign	0.44	T
Sift4G	Benign	0.50	T
Polyphen		0.0010	B
Vest4		0.32
MVP		0.068
MPC		0.048
ClinPred		0.0032	T
GERP RS		-0.66
Varity_R		0.038
gMVP		0.19
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs148939821; hg19: chr7-11446574; COSMIC: COSV69855580; COSMIC: COSV69855580;