6-26407917-T-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_007048.6(BTN3A1):c.680T>A(p.Leu227His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00308 in 1,614,224 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (15 hom.)
• Consequence: BTN3A1 NM_007048.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.19

Genes affected

BTN3A1 (HGNC:1138): (butyrophilin subfamily 3 member A1) The butyrophilin (BTN) genes are a group of major histocompatibility complex (MHC)-associated genes that encode type I membrane proteins with 2 extracellular immunoglobulin (Ig) domains and an intracellular B30.2 (PRYSPRY) domain. Three subfamilies of human BTN genes are located in the MHC class I region: the single-copy BTN1A1 gene (MIM 601610) and the BTN2 (e.g., BTN2A1; MIM 613590) and BTN3 (e.g., BNT3A1) genes, which have undergone tandem duplication, resulting in 3 copies of each (summary by Smith et al., 2010 [PubMed 20208008]).[supplied by OMIM, Nov 2010]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01064983).
• BP6: Variant 6-26407917-T-A is Benign according to our data. Variant chr6-26407917-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 770726.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTN3A1	NM_007048.6	c.680T>A	p.Leu227His	missense_variant	4/10	ENST00000289361.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTN3A1	ENST00000289361.11	c.680T>A	p.Leu227His	missense_variant	4/10	1	NM_007048.6	P1
	ENST00000707189.1	n.1000-145270T>A		intron_variant, non_coding_transcript_variant
	ENST00000707191.1	n.1001-124788T>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00243 AC: 370 AN: 152234 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.00273

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00394

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00298 AC: 749 AN: 251172 Hom.: 1 AF XY: 0.00316 AC XY: 429 AN XY: 135744

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.000954

Gnomad ASJ exome AF: 0.00159

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00487

Gnomad FIN exome AF: 0.00263

Gnomad NFE exome AF: 0.00410

Gnomad OTH exome AF: 0.00326

GnomAD4 exome AF: 0.00315 AC: 4604 AN: 1461872 Hom.: 15 Cov.: 31 AF XY: 0.00323 AC XY: 2348 AN XY: 727242

Gnomad4 AFR exome AF: 0.000388

Gnomad4 AMR exome AF: 0.00112

Gnomad4 ASJ exome AF: 0.000995

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00463

Gnomad4 FIN exome AF: 0.00339

Gnomad4 NFE exome AF: 0.00334

Gnomad4 OTH exome AF: 0.00310

GnomAD4 genome AF: 0.00244 AC: 371 AN: 152352 Hom.: 0 Cov.: 32 AF XY: 0.00235 AC XY: 175 AN XY: 74504

Gnomad4 AFR AF: 0.000505

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00352

Gnomad4 FIN AF: 0.00273

Gnomad4 NFE AF: 0.00394

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00351 Hom.: 2

Bravo AF: 0.00231

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.00156 AC: 6

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00407 AC: 35

ExAC AF: 0.00328 AC: 398

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00502

EpiControl AF: 0.00468

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.28
Cadd	Benign	19
Dann	Uncertain	0.98
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.032	N
LIST_S2	Uncertain	0.90	D;D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.011	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Pathogenic	3.2	M;M;M;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-5.4	D;D;D;D
REVEL	Benign	0.040
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D
Polyphen		1.0	D;D;D;.
Vest4		0.61
MVP		0.62
MPC		0.41
ClinPred		0.12	T
GERP RS		0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.31
gMVP		0.31

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

Publications

LitVar

Other links and lift over

dbSNP: rs144114619; hg19: chr6-26408145; COSMIC: COSV99175746; COSMIC: COSV99175746;