rs143861053

Variant names:

• chr1-177276259-C-T
• rs143861053
• NM_021165.4:c.837C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_021165.4(BRINP2):​c.837C>T​(p.Tyr279Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00197 in 1,614,214 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0021 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0020 (74 hom.)
• Consequence: BRINP2 NM_021165.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.29
• Publications: 2 publications found

Genes affected

BRINP2 (HGNC:13746): (BMP/retinoic acid inducible neural specific 2) Predicted to be involved in cellular response to retinoic acid; negative regulation of mitotic cell cycle; and positive regulation of neuron differentiation. Predicted to be located in extracellular region. Predicted to be active in dendrite; endoplasmic reticulum; and neuronal cell body. Implicated in oral squamous cell carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 1-177276259-C-T is Benign according to our data. Variant chr1-177276259-C-T is described in ClinVar as Benign. ClinVar VariationId is 770119.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.29 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00207 (316/152376) while in subpopulation AMR AF = 0.0174 (267/15310). AF 95% confidence interval is 0.0157. There are 4 homozygotes in GnomAd4. There are 174 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021165.4. 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
	BRINP2	NM_021165.4	MANE Select	c.837C>T	p.Tyr279Tyr	synonymous	Exon 6 of 8	NP_066988.1	Q9C0B6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRINP2	ENST00000361539.5	TSL:1 MANE Select	c.837C>T	p.Tyr279Tyr	synonymous	Exon 6 of 8	ENSP00000354481.4	Q9C0B6-1
	BRINP2	ENST00000944009.1		c.888C>T	p.Tyr296Tyr	synonymous	Exon 6 of 8	ENSP00000614068.1
	BRINP2	ENST00000907915.1		c.837C>T	p.Tyr279Tyr	synonymous	Exon 7 of 9	ENSP00000577974.1

Frequencies

GnomAD3 genomes AF: 0.00207 AC: 315 AN: 152258 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.000313

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0174

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00805 AC: 2023 AN: 251380 AF XY: 0.00577

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.0562

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000334

Gnomad OTH exome AF: 0.00472

GnomAD4 exome AF: 0.00196 AC: 2859 AN: 1461838 Hom.: 74 Cov.: 31 AF XY: 0.00161 AC XY: 1173 AN XY: 727224

African (AFR) AF: 0.000269 AC: 9 AN: 33480

American (AMR) AF: 0.0508 AC: 2273 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000278 AC: 24 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.000426 AC: 474 AN: 1112008

Other (OTH) AF: 0.00124 AC: 75 AN: 60396

GnomAD4 genome AF: 0.00207 AC: 316 AN: 152376 Hom.: 4 Cov.: 33 AF XY: 0.00234 AC XY: 174 AN XY: 74512

African (AFR) AF: 0.000313 AC: 13 AN: 41596

American (AMR) AF: 0.0174 AC: 267 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.000367 AC: 25 AN: 68038

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.000975 Hom.: 0

Bravo AF: 0.00481

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000652

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	-0.41
CADD	Benign	6.1
DANN	Benign	0.49
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs143861053; hg19: chr1-177245395;