19-9214342-A-G

Variant names:

• chr19-9214342-A-G
• rs116460228
• NM_001005191.3:c.496T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001005191.3(OR7D4):​c.496T>C​(p.Leu166Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00263 in 1,614,004 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (55 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (44 hom.)
• Consequence: OR7D4 NM_001005191.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.600
• Publications: 4 publications found

Genes affected

OR7D4 (HGNC:8380): (olfactory receptor family 7 subfamily D member 4) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

OR7E24 (HGNC:8396): (olfactory receptor family 7 subfamily E member 24) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 19-9214342-A-G is Benign according to our data. Variant chr19-9214342-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 777413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0135 (2059/152196) while in subpopulation AFR AF = 0.0471 (1956/41502). AF 95% confidence interval is 0.0454. There are 55 homozygotes in GnomAd4. There are 943 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 55 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005191.3. 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
	OR7D4	NM_001005191.3	MANE Select	c.496T>C	p.Leu166Leu	synonymous	Exon 2 of 2	NP_001005191.1	Q8NG98

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR7D4	ENST00000641669.1	MANE Select	c.496T>C	p.Leu166Leu	synonymous	Exon 2 of 2	ENSP00000493383.1	Q8NG98
	OR7D4	ENST00000308682.3	TSL:6	c.496T>C	p.Leu166Leu	synonymous	Exon 1 of 1	ENSP00000310488.2	Q8NG98
	OR7D4	ENST00000641244.1		c.496T>C	p.Leu166Leu	synonymous	Exon 2 of 2	ENSP00000493404.1	Q8NG98

Frequencies

GnomAD3 genomes AF: 0.0135 AC: 2052 AN: 152078 Hom.: 55 Cov.: 32

Gnomad AFR AF: 0.0471

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0129

GnomAD2 exomes AF: 0.00399 AC: 1003 AN: 251444 AF XY: 0.00280

Gnomad AFR exome AF: 0.0527

Gnomad AMR exome AF: 0.00312

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000264

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.00150 AC: 2190 AN: 1461808 Hom.: 44 Cov.: 33 AF XY: 0.00125 AC XY: 908 AN XY: 727218

African (AFR) AF: 0.0473 AC: 1580 AN: 33432

American (AMR) AF: 0.00322 AC: 144 AN: 44722

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

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86256

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

Middle Eastern (MID) AF: 0.00434 AC: 25 AN: 5766

European-Non Finnish (NFE) AF: 0.000166 AC: 185 AN: 1111982

Other (OTH) AF: 0.00396 AC: 239 AN: 60394

GnomAD4 genome AF: 0.0135 AC: 2059 AN: 152196 Hom.: 55 Cov.: 32 AF XY: 0.0127 AC XY: 943 AN XY: 74420

African (AFR) AF: 0.0471 AC: 1956 AN: 41502

American (AMR) AF: 0.00327 AC: 50 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68018

Other (OTH) AF: 0.0128 AC: 27 AN: 2112

Alfa AF: 0.00736 Hom.: 11

Bravo AF: 0.0156

EpiCase AF: 0.000491

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Likely 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	-0.89
CADD	Benign	2.6
DANN	Benign	0.28
PhyloP100		-0.60
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs116460228; hg19: chr19-9325018; COSMIC: COSV58071348; COSMIC: COSV58071348;