chr7-22493719-A-C

Variant names:

• chr7-22493719-A-C
• rs144007277
• NM_001382447.1:c.202T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001382447.1(STEAP1B):​c.202T>G​(p.Phe68Val) variant causes a missense change. The variant allele was found at a frequency of 0.00208 in 1,613,986 control chromosomes in the GnomAD database, including 68 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F68L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.011 (27 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (41 hom.)
• Consequence: STEAP1B NM_001382447.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.04
• Publications: 5 publications found

Genes affected

STEAP1B (HGNC:41907): (STEAP family member 1B) Predicted to be integral component of membrane. Predicted to be active in endosome and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009422809).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0108 (1651/152336) while in subpopulation AFR AF = 0.0379 (1577/41568). AF 95% confidence interval is 0.0364. There are 27 homozygotes in GnomAd4. There are 774 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 27 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382447.1. 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
	STEAP1B	NM_001382447.1	MANE Select	c.202T>G	p.Phe68Val	missense	Exon 3 of 5	NP_001369376.1	A0A7I2V339
	STEAP1B	NM_001164460.2		c.202T>G	p.Phe68Val	missense	Exon 3 of 5	NP_001157932.1	Q6NZ63-2
	STEAP1B	NM_207342.3		c.145T>G	p.Phe49Val	missense	Exon 3 of 5	NP_997225.1	Q6NZ63-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STEAP1B	ENST00000678116.1	MANE Select	c.202T>G	p.Phe68Val	missense	Exon 3 of 5	ENSP00000503251.1	A0A7I2V339
	STEAP1B	ENST00000404369.8	TSL:1	c.202T>G	p.Phe68Val	missense	Exon 3 of 5	ENSP00000384370.4	Q6NZ63-2
	STEAP1B	ENST00000406890.6	TSL:1	c.145T>G	p.Phe49Val	missense	Exon 3 of 5	ENSP00000385239.2	Q6NZ63-1

Frequencies

GnomAD3 genomes AF: 0.0107 AC: 1636 AN: 152218 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.0377

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00340

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00813

GnomAD2 exomes AF: 0.00277 AC: 695 AN: 251166 AF XY: 0.00211

Gnomad AFR exome AF: 0.0394

Gnomad AMR exome AF: 0.00130

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.00117 AC: 1709 AN: 1461650 Hom.: 41 Cov.: 31 AF XY: 0.00102 AC XY: 739 AN XY: 727130

African (AFR) AF: 0.0439 AC: 1468 AN: 33472

American (AMR) AF: 0.00136 AC: 61 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5762

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1111830

Other (OTH) AF: 0.00255 AC: 154 AN: 60376

GnomAD4 genome AF: 0.0108 AC: 1651 AN: 152336 Hom.: 27 Cov.: 32 AF XY: 0.0104 AC XY: 774 AN XY: 74504

African (AFR) AF: 0.0379 AC: 1577 AN: 41568

American (AMR) AF: 0.00340 AC: 52 AN: 15302

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68030

Other (OTH) AF: 0.00804 AC: 17 AN: 2114

Alfa AF: 0.00326 Hom.: 8

Bravo AF: 0.0122

ESP6500AA AF: 0.0419 AC: 58

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00341 AC: 414

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.19
Eigen_PC	Benign	-0.014
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.81	T
MetaRNN	Benign	0.0094	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		6.0
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Benign	0.10
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.94	P
Vest4		0.70
MVP		0.048
MPC		0.74
ClinPred		0.10	T
GERP RS		1.1
Varity_R		0.46
gMVP		0.71
Mutation Taster		=69/31	polymorphism

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: rs144007277; hg19: chr7-22533338;