rs35115415

Variant names:

• chr17-48529751-C-T
• rs35115415
• NM_002144.4:c.702G>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_002144.4(HOXB1):​c.702G>A​(p.Val234Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00416 in 1,611,082 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0031 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0043 (14 hom.)
• Consequence: HOXB1 NM_002144.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.56
• Publications: 4 publications found

Genes affected

HOXB1 (HGNC:5111): (homeobox B1) This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms. Mammals possess four similar homeobox gene clusters, HOXA, HOXB, HOXC and HOXD, located on different chromosomes, consisting of 9 to 11 genes arranged in tandem. This gene is one of several homeobox HOXB genes located in a cluster on chromosome 17. [provided by RefSeq, Jul 2008]

HOXB1 Gene-Disease associations (from GenCC):

• facial paresis, hereditary congenital, 3

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• congenital hereditary facial paralysis-variable hearing loss syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000294508 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 17-48529751-C-T is Benign according to our data. Variant chr17-48529751-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 701967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.56 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 14 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002144.4. 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
	HOXB1	NM_002144.4	MANE Select	c.702G>A	p.Val234Val	synonymous	Exon 2 of 2	NP_002135.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXB1	ENST00000239174.7	TSL:1 MANE Select	c.702G>A	p.Val234Val	synonymous	Exon 2 of 2	ENSP00000355140.5	P14653-1
	HOXB1	ENST00000577092.1	TSL:6	c.*455G>A		3_prime_UTR	Exon 1 of 1	ENSP00000459066.1	P14653-2
	ENSG00000294508	ENST00000724000.1		n.817+1378C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00306 AC: 466 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000579

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00405

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00529

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00336 AC: 839 AN: 249470 AF XY: 0.00339

Gnomad AFR exome AF: 0.000738

Gnomad AMR exome AF: 0.00176

Gnomad ASJ exome AF: 0.000596

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00538

Gnomad NFE exome AF: 0.00499

Gnomad OTH exome AF: 0.00343

GnomAD4 exome AF: 0.00427 AC: 6235 AN: 1458784 Hom.: 14 Cov.: 34 AF XY: 0.00420 AC XY: 3050 AN XY: 725868

African (AFR) AF: 0.000657 AC: 22 AN: 33480

American (AMR) AF: 0.00166 AC: 74 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.000536 AC: 14 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.00199 AC: 172 AN: 86254

European-Finnish (FIN) AF: 0.00472 AC: 238 AN: 50450

Middle Eastern (MID) AF: 0.00208 AC: 12 AN: 5766

European-Non Finnish (NFE) AF: 0.00488 AC: 5429 AN: 1111928

Other (OTH) AF: 0.00452 AC: 273 AN: 60366

GnomAD4 genome AF: 0.00305 AC: 465 AN: 152298 Hom.: 0 Cov.: 32 AF XY: 0.00282 AC XY: 210 AN XY: 74472

African (AFR) AF: 0.000553 AC: 23 AN: 41558

American (AMR) AF: 0.00124 AC: 19 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4832

European-Finnish (FIN) AF: 0.00405 AC: 43 AN: 10630

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

European-Non Finnish (NFE) AF: 0.00529 AC: 360 AN: 68016

Other (OTH) AF: 0.00427 AC: 9 AN: 2110

Alfa AF: 0.00403 Hom.: 0

Bravo AF: 0.00271

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00502

EpiControl AF: 0.00427

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	11
DANN	Benign	0.85
PhyloP100		1.6
Mutation Taster		=89/11	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: rs35115415; hg19: chr17-46607113;