chr16-59290-G-A

Variant names:

• chr16-59290-G-A
• rs116064244
• NM_022450.5:c.1953C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_022450.5(RHBDF1):​c.1953C>T​(p.Asp651Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00191 in 1,611,400 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (22 hom., cov: 33)
  • Exomes 𝑓: 0.0010 (36 hom.)
• Consequence: RHBDF1 NM_022450.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.78
• Publications: 0 publications found

Genes affected

RHBDF1 (HGNC:20561): (rhomboid 5 homolog 1) Predicted to enable growth factor binding activity and serine-type endopeptidase activity. Involved in several processes, including negative regulation of protein secretion; regulation of epidermal growth factor receptor signaling pathway; and regulation of proteasomal protein catabolic process. Located in Golgi membrane and endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 16-59290-G-A is Benign according to our data. Variant chr16-59290-G-A is described in ClinVar as Benign. ClinVar VariationId is 711634.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.78 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0101 (1546/152318) while in subpopulation AFR AF = 0.0347 (1442/41554). AF 95% confidence interval is 0.0332. There are 22 homozygotes in GnomAd4. There are 748 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 22 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022450.5. 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
	RHBDF1	NM_022450.5	MANE Select	c.1953C>T	p.Asp651Asp	synonymous	Exon 16 of 18	NP_071895.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHBDF1	ENST00000262316.10	TSL:1 MANE Select	c.1953C>T	p.Asp651Asp	synonymous	Exon 16 of 18	ENSP00000262316.5	Q96CC6
	RHBDF1	ENST00000944434.1		c.2061C>T	p.Asp687Asp	synonymous	Exon 17 of 19	ENSP00000614493.1
	RHBDF1	ENST00000944435.1		c.2061C>T	p.Asp687Asp	synonymous	Exon 17 of 19	ENSP00000614494.1

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1543 AN: 152200 Hom.: 23 Cov.: 33

Gnomad AFR AF: 0.0347

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00530

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00860

GnomAD2 exomes AF: 0.00260 AC: 644 AN: 247842 AF XY: 0.00190

Gnomad AFR exome AF: 0.0363

Gnomad AMR exome AF: 0.00131

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000358

Gnomad OTH exome AF: 0.00132

GnomAD4 exome AF: 0.00105 AC: 1526 AN: 1459082 Hom.: 36 Cov.: 34 AF XY: 0.000879 AC XY: 638 AN XY: 725638

African (AFR) AF: 0.0377 AC: 1262 AN: 33456

American (AMR) AF: 0.00150 AC: 67 AN: 44576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25918

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.0000350 AC: 3 AN: 85814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53050

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5758

European-Non Finnish (NFE) AF: 0.0000369 AC: 41 AN: 1110544

Other (OTH) AF: 0.00244 AC: 147 AN: 60282

GnomAD4 genome AF: 0.0101 AC: 1546 AN: 152318 Hom.: 22 Cov.: 33 AF XY: 0.0100 AC XY: 748 AN XY: 74488

African (AFR) AF: 0.0347 AC: 1442 AN: 41554

American (AMR) AF: 0.00529 AC: 81 AN: 15302

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68036

Other (OTH) AF: 0.00851 AC: 18 AN: 2114

Alfa AF: 0.00783 Hom.: 7

Bravo AF: 0.0124

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	11
DANN	Benign	0.87
PhyloP100		2.8
PromoterAI		-0.050	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs116064244; hg19: chr16-109288;